Protokol kemoterapi

THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST

CHEMOTHERAPY PROTOCOLS

V10.0

Issue Date:

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30 October 2012

Author: Dr. D.B. Smith Smith

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Filename:

Authorised by: Dr. Dr. D.B. Smith

MCHACPROTO

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CCC Chemotherapy Protocols

2012

General observations observations ................................................................... .................................................................................................................................5 ..............................................................5 Protocol Additions 2012.............................................................................................................................5 Cancer Drugs Fund ...................................................................... ...................................................................................................................................5 .............................................................5 Off Protocol Treatment Policy .................................................................. ...................................................................................................................5 .................................................5 Trials..........................................................................................................................................................5 Co-payments / top-ups / additional private care........................................................................................5 Dose Capping............................................................................................................................................6

Breast Cancer.............................................................................................................................................. Cancer.............................................................................................................................................. 7 Adjuvant.....................................................................................................................................................7 Adjuvant.......................................................................................................... ...........................................7 Neo-adjuvant ................................................................... ......................................................................................................................................... ........................................................................ .. 11 Advanced disease ........................................................................ ...................................................................................................................................12 ...........................................................12 Patients with compromised liver or marrow function...............................................................................16 Bone directed therapy .................................................................. .............................................................................................................................18 ...........................................................18 Management of patients with HER2 positive cancers.............................................................................19

Gastrointestinal Gastrointestinal Cancer.................................................................................. Cancer............................................................................................................................21 ..........................................21 Oesophageal Carcinoma.........................................................................................................................21 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 21 Neoadjuvant.........................................................................................................................................21 Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma ...............................................24 Neoadjuvant / Adjuvant........................................................................................................................24 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 24 Pancreatic cancer....................................................................................................................................28 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 28 Cholangiocarcinoma / Gall Bladder Carcinoma ................................................................... ...................................................................................... ................... 31 Advanced ..................................................................... ........................................................................................................................................... ........................................................................ .. 31 Hepatocellular carcinoma* ....................................................................... ......................................................................................................................33 ...............................................33 Neuroendocrine tumours.........................................................................................................................34 Colorectal ......................................................................... .............................................................................................................................................. ....................................................................... .. 36 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 36 Rectal cancer - Chemoradiation..............................................................................................................38 Advanced Colorectal Cancer............................................................................................................... Cancer................................................................................................................... .... 39 Anal Carcinoma ............................................................... ..................................................................................................................................... ........................................................................ .. 47

Gynaecological Gynaecological Cancer Cancer ................................................................ ............................................................................................................................49 ............................................................49 Epithelial Ovarian Cancer........................................................................................................................49 Epithelial Ovarian Cancer – Mucinous Histology ................................................................. .................................................................................... ................... 56 Endometrial Carcinoma...........................................................................................................................58 Cervical Cancer ............................................................... ..................................................................................................................................... ........................................................................ .. 60 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 60

Haematological Haematological Malignancies Malignancies ................................................................... ..................................................................................................................65 ...............................................65 Issue Date:

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CCC Chemotherapy Protocols

2012

General observations observations ................................................................... .................................................................................................................................5 ..............................................................5 Protocol Additions 2012.............................................................................................................................5 Cancer Drugs Fund ...................................................................... ...................................................................................................................................5 .............................................................5 Off Protocol Treatment Policy .................................................................. ...................................................................................................................5 .................................................5 Trials..........................................................................................................................................................5 Co-payments / top-ups / additional private care........................................................................................5 Dose Capping............................................................................................................................................6

Breast Cancer.............................................................................................................................................. Cancer.............................................................................................................................................. 7 Adjuvant.....................................................................................................................................................7 Adjuvant.......................................................................................................... ...........................................7 Neo-adjuvant ................................................................... ......................................................................................................................................... ........................................................................ .. 11 Advanced disease ........................................................................ ...................................................................................................................................12 ...........................................................12 Patients with compromised liver or marrow function...............................................................................16 Bone directed therapy .................................................................. .............................................................................................................................18 ...........................................................18 Management of patients with HER2 positive cancers.............................................................................19

Gastrointestinal Gastrointestinal Cancer.................................................................................. Cancer............................................................................................................................21 ..........................................21 Oesophageal Carcinoma.........................................................................................................................21 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 21 Neoadjuvant.........................................................................................................................................21 Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma ...............................................24 Neoadjuvant / Adjuvant........................................................................................................................24 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 24 Pancreatic cancer....................................................................................................................................28 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 28 Cholangiocarcinoma / Gall Bladder Carcinoma ................................................................... ...................................................................................... ................... 31 Advanced ..................................................................... ........................................................................................................................................... ........................................................................ .. 31 Hepatocellular carcinoma* ....................................................................... ......................................................................................................................33 ...............................................33 Neuroendocrine tumours.........................................................................................................................34 Colorectal ......................................................................... .............................................................................................................................................. ....................................................................... .. 36 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 36 Rectal cancer - Chemoradiation..............................................................................................................38 Advanced Colorectal Cancer............................................................................................................... Cancer................................................................................................................... .... 39 Anal Carcinoma ............................................................... ..................................................................................................................................... ........................................................................ .. 47

Gynaecological Gynaecological Cancer Cancer ................................................................ ............................................................................................................................49 ............................................................49 Epithelial Ovarian Cancer........................................................................................................................49 Epithelial Ovarian Cancer – Mucinous Histology ................................................................. .................................................................................... ................... 56 Endometrial Carcinoma...........................................................................................................................58 Cervical Cancer ............................................................... ..................................................................................................................................... ........................................................................ .. 60 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 60

Haematological Haematological Malignancies Malignancies ................................................................... ..................................................................................................................65 ...............................................65 Issue Date:

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Hodgkins disease ......................................................................... ....................................................................................................................................65 ...........................................................65 Non-Hodgkins Lymphoma.......................................................................................................................67

Head and Neck Neck Cancer ................................................................. .............................................................................................................................72 ............................................................72 Nasopharyngeal Carcinoma....................................................................................................................75 Thyroid Cancer ................................................................ ...................................................................................................................................... ........................................................................ .. 76

Lung Cancer Cancer ....................................................................... ............................................................................................................................................ ....................................................................... .. 77 Small Cell ......................................................................... .............................................................................................................................................. ....................................................................... .. 77 Non-Small Cell Lung Cancer...................................................................................................................80

Mesothelioma .................................................................... .......................................................................................................................................... ........................................................................ .. 87 Melanoma...................................................................................................................................................88 Sarcomas Sarcomas ............................................................... ..................................................................................................................................... .................................................................................... .............. 89 Soft Tissue Sarcoma Sarcoma .................................................................... ...............................................................................................................................89 ...........................................................89 Adjuvant ....................................................................... ............................................................................................................................................. ........................................................................ .. 89 Neo-adjuvant........................................................................................................................................89 Osteosarcoma / MFH of of bone / Leiomyosarcoma Leiomyosarcoma of Bone .............................................................. ..................................................................... ....... 91 Advanced Osteosarcoma ......................................................................... ........................................................................................................................93 ...............................................93 Ewings Sarcoma......................................................................................................................................94 Neoadjuvant.........................................................................................................................................94 Aggressive fibromatosis .............................................................. ..........................................................................................................................99 ............................................................99 Rhabdomyosarcoma ................................................................... ...............................................................................................................................99 ............................................................99 IVADo Regime for High Risk Rhabdomyosarcoma...............................................................................101 Gastro-intestinal Stromal Tumours (GIST)............................................................................................103

Urological Cancer ............................................................. ...................................................................................................................................104 ......................................................................104 Bladder Cancer - Transitional cell .................................................................... ......................................................................................................... ..................................... 104 Renal cancer ................................................................... .........................................................................................................................................108 ......................................................................108 Prostate Cancer.....................................................................................................................................111 Germ Cell Cell Tumours ...................................................................... ...............................................................................................................................113 .........................................................113 Adjuvant ....................................................................... .............................................................................................................................................113 ......................................................................113

Primary CNS Malignancy Malignancy .......................................................................... .......................................................................................................................117 .............................................117 Adjuvant Temozolomide ...................................................................... ....................................................................................................................117 ..............................................117

Primary CNS Lymphoma.............................................................. Lymphoma ........................................................................................................................121 ..........................................................121 Adenocarcinoma Adenocarcinoma of Unknown Primary Origin .............................................................. ..................................................................................... ....................... 124 CCC Emergency Chemotherapy Chemotherapy Drugs ...................................................................... ................................................................................................ .......................... 125 Bone Metastases............................................................... Metastases.....................................................................................................................................126 ......................................................................126 CCC anti-emetic guidelines for cytotoxic chemotherapy chemotherapy .............................................................. ................................................................... ..... 127 GCSF ...................................................................... ............................................................................................................................................ .................................................................................. ............ 130 Primary Prophylaxis...............................................................................................................................130 Secondary Prophylaxis............................................................................................... Prophylaxis.......................................................................................................................... ........................... 130

Erythropoietin..........................................................................................................................................132 Intrathecal Intrathecal (IT) Chemotherapy Chemotherapy .................................................................. ...............................................................................................................133 .............................................133 Creatinine Clearance ..................................................................... ..............................................................................................................................134 .........................................................134 Issue Date:

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Calvert formula for Carboplatin dosage ............................................................................................... 134 Cisplatin dose guidelines....................................................................................................................... 134 Cisplatin Hydration Policy...................................................................................................................... 135 Haematological Indices – Guidelines for the administration of chemotherapy ...............................136 Capecitabine-...........................................................................................................................................136 Renal function recommendations .........................................................................................................136 Neutropenic Sepsis Policy.....................................................................................................................137 Platelet Transfusion Policy ....................................................................................................................138 Hypocalcaemia ........................................................................................................................................138 Hypomagnesaemia .................................................................................................................................138 Ifosfamide Encephalopathy and Methylene Blue ................................................................................ 139 Ifosfamide Renal Toxicity.......................................................................................................................139 Folinic acid rescue for High Dose Methotrexate ................................................................................. 140 CCC Dose Banding Policy...................................................................................................................... 140 Surface Area Nomogram........................................................................................................................ 148

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General observations There is now an electronic version of the protocol book which is available on CCO Comms and the CCC internet site. This will be updated as required during the year and represents the working version of the book. The paper version will continue but will only be updated annually.

Protocol Additions 2012 Maintenance pemetrexed in advanced NSCLC

Pazopanib in advanced renal cell carcinoma

Gefitinib in advanced NSCLC

In addition we have included all drugs currently funded by the Cancer Drugs Fund. Please refer to the NW Cancer Drugs Fund website for the latest funding policy and conditions for approval. Please note that there may be a 90 day period before a NICE approved drug is funded routinely and

therefore

doesn’t need a CDF application.;

Cancer Drugs Fund A number of treatments are now available via the Cancer Drugs Fund. T he process for accessing the fund is as follows:

•

Complete the relevant application form which can be found on the North West Cancer Drugs Fund web site. The easiest way to find this is to type “ nw cancer drugs fund ” into google and select the application forms button in the header on the home page.

•

E-mail the completed form to the pharmacy dept at CCC using: [email protected] this address can be found by typing cco pharmacists into the address book in outlook.

Off Protocol Treatment Policy Inevitably situations will arise that are not covered by the standard CCC protocols. Consultants who wish to use a non-protocol regimen should complete the non-protocol treatment form and submit it to the Clinical Director for Chemotherapy for approval at least 5 days prior to the date of cycle 1 of the proposed treatment. All reasonable requests will be granted.

Trials Entry to clinical trials should be considered for all patients but individual studies have not been listed due to frequent changes.

Co-payments / top-ups / additional private care The uptake of co-payments has been minimal and has been further reduced by the introduction of the Cancer Drugs Fund. However the process is still in place and is outlined below. Issue Date:

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Co-payment refers to top-up funding by an NHS patient for an otherwise unavailable treatment. NHS policy allows patients to fund elements of their care not currently available on the NHS without losing their entitlement to continue with free NHS care.

The CCC co-payments policy considers access to systemic cancer treatments - chemotherapy or targeted therapies - that are currently not funded for use in NHS patients. A copy of the policy can be obtained from pharmacy or found on the CCC website and includes all the required documentation:

•

Co-payment algorithm

•

Additional Private Treatment Form

•

Patient information leaflet.

•

Financial agreement forms.

The self-funded drug may be a single agent or given in combination with standard treatments, in which case the costs incurred relate only to the self-funded drug. However it should always be clear which components of treatment are privately funded and which are provided as NHS treatments.

The patient commits to self-funding the treatment for the duration of the entire programme under supervision by the responsible consultant i.e. a specific number of cycles or indefinite period while there is evidence of a maintained benefit and response. This will include the costs of treatment preparation and delivery, payment of any investigations needed, and any supportive care drugs given as a direct consequence of receiving the self-funded treatment.

Dose Capping In line with ASCO guidelines we have removed routine dose capping for patients with a surface area in 2

excess of 2m .

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Breast Cancer Adjuvant Epi-CMF 2

Epirubicin 100mg/m IV day 1 repeated at 21 day intervals x 4 cycles

followed by CMF x 4 cycles

Laboratory Investigations •

Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated

CMF

•

Where renal / hepatic function are abnormal treatment is at physician discretion

•

LV ejection fraction prior to cycle 1 if history of cardiac problems

•

FBC prior to each cycle. 2

Cyclophosphamide

100mg/m po

Methotrexate

40mg/m IV

Fluorouracil

600mg/m IV

2

days 1-14 in divided doses days 1 and 8

2

days 1 and 8

For patients unable to tolerate oral cyclophosphamide substitute 2

IV cyclophosphamide 600mg/m days 1 and 8

Folinic acid rescue not normally required unless patients develop signs of Methotrexate toxicity, then 15mg 6 hourly x 6 doses starting 24hrs post Methotrexate with subsequent cycles

Cycles are repeated at 28 days from day 1 to a total of 6 cycles.



•

Where renal / hepatic function are abnormal treatment is at physician discretion but Methotrexate is hazardous in the presence of renal insufficiency

•

FBC prior to each cycle, not required on day 8

•

Standard FBC limits for administration apply 2

AC

2

Doxorubicin 60mg/m + cyclophosphamide 600mg/m IV day 1 repeated at 21 day intervals for 4 cycles has been shown to be equivalent to 6 cycles of CMF.

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•


•


•

FBC prior to each cycle

•


2

EC Epirubicin 90mg/m IV + cyclophosphamide 600mg/m IV day 1 repeated at 21 day intervals for 4 cycles. Alternative to AC in this situation



•


•


•


•

Standard FBC limits for administration apply

FEC / Docetaxel This protocol is available for node positive or high risk node negative patients.

Patients should receive primary prophylaxis with pegfilgrastim after each cycle

FEC

2

Fluorouracil

500mg/m IV day 1

Epirubicin

100mg/m IV day 1

Cyclophosphamide

500mg/m IV day 1

2 2

Repeat at 21 day intervals for 3 cycles



•


•


•


•


Followed by

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2

Docetaxel 100 mg/m IV x 3 cycles at 21 day intervals

Pre-medication: Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel



•


•


•


NB: See section on advanced disease for dose modifications and precautions .

Trastuzumab For patients with HER2 positive cancers

•

Non-metastatic potentially operable primary invasive breast cancer

•

HER2 positive (IHC 3+ and / or FISH positive)

•

Completed definitive surgery and radiotherapy

•

Completed at least 4 cycles of adjuvant or neoadjuvant chemotherapy

•

Within 9 weeks of chemotherapy / radiotherapy / surgery, whichever is last.

•

ECOG PS 0 or 1

•

Baseline LVEF normal after completing anthracycline chemotherapy

•

No serious cardiac illness

Trastuzumab

8mg/kg IV loading dose over 90min then 6mg/kg over 60min and thereafter over 30 min every 3 weeks for 12 months (18 cycles) if no problems. May be given concurrently with docetaxel.

Stop at any time if CCF develops

LVEF at 3, 6, 9 and 12 months Stop trastuzumab if LVEF falls by 10 points or to <50% Repeat after 3-4 weeks and if LVEF: 50+ continue with trastuzumab

•

44-49 and within 10 points of baseline continue with trastuzumab

•

< 44 stop trastuzumab

•

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In patients at significant risk of cardiac problems:

HER2 negative

TC

2

Docetaxel

75mg/m IV

Cyclophosphamide

600mg/m IV

2

Repeat at 21 day intervals for 4-6 cycles



•


•


•


•


HER2 positive

TCH

2

Docetaxel

75mg/m IV

Carboplatin AUC6

Trastuzumab 8mg/kg iv loading dose over 90min then 6mg/kg over 60min and thereafter over 30 min every 3 weeks for 12 months (18 cycles) if no problems commencing with first cycle of chemotherapy



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Neo-adjuvant Indication / Treatment plan Patients with locally advanced disease or to allow less radical surgery in patients with operable tumours.

Options include six cycles of EC/AC or four cycles EC/AC followed by four cycles docetaxel at 100mg/m

2

HER-2 positive patients may commence trastuzumab following completion of anthracycline based treatment i.e. concurrently with docetaxel if this is being given provided LVEF normal after completion of the anthracycline. Patients should then have the remaining 14 cycles of trastuzumab as adjuvant treatment.

Patients should receive primary prophylaxis with pegfilgrastim after each cycle

AC/EC

Doxorubicin

2

60mg/m IV day 1 or 2

Epirubicin

90mg/m IV day 1 +

Cyclophosphamide

2

600mg/m IV day 1

Repeat at 21 day intervals for up to 6 cycles.



•


•


•


•


Docetaxel

100 mg/m IV q 21 days x 4 cycles

Pre-medication:

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Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel

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•


•


NB: See section on advanced disease for dose modifications and precautions .

Advanced disease First line Doxorubicin

2

75mg/m IV day 1

Repeat at 21 day intervals usually to a maximum of 6 cycles

AC/EC

Doxorubicin

2

50mg/m IV

day 1

or Epirubicin Cyclophosphamide

2

90mg/m IV

day1

2

500mg/m IV

day 1

Repeat at 21 day intervals usually to a maximum of 6 cycles



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2

Docetaxel

75-100 mg/m IV day 1 q 21 days, max 6 cycles

Pre-medication:

Dexamethasone 8mg oral bd x 3 days start 24hrs pre-docetaxel

Criteria

•

Previously received full dose anthracycline as adjuvant therapy or

•

Less than six months since anthracycline based adjuvant therapy or

•

Unsuitable for anthracycline therapy nd

rd

NB: See section on 2 /3 line treatment for dose modifications and precautions .



•


•


•


Docetaxel / Capecitabine Docetaxel

2

75mg/m IV day 1 +

Capecitabine

2

1000mg/m bd oral days 1-14

NB see capecitabine renal function recommendations p130

Pre-medication

Dexamethasone 8mg bd x 3 days start 24hrs pre-docetaxel

Repeat at 21 day intervals, max 6 cycles

Criteria

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PS 0-1 NB very fit patients only

•

Recurrent following adjuvant anthracycline therapy

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•


•


Paclitaxel / Gemcitabine 2

Paclitaxel

175mg/m IV

day 1

Gemcitabine

1250mg/m IV

days 1 and 8

Pre-medication

Chlorphenamine

10mg

Dexamethasone

16mg

Ranitidine

50mg

2


Criteria •

PS 0-1 NB very fit patients only

•

Recurrent following adjuvant anthracycline therapy



•


•


•


*Bevacizumab

10mg/kg IV infusion

Repeat at 14 day intervals

Criteria Advanced disease Triple negative First line chemotherapy In combination with paclitaxel

*NB available via the Cancer Drugs fund

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2

*Eribulin 1.23mg/m eribulin mesylate IV days 1 and 8 of a 21 day cycle

Criteria At least 2 prior chemotherapy regimens for advanced disease Evidence of response to prior chemotherapy


Everolimus + exemestane Everolimus 10mg oral daily

Exemestane 25mg oral daily

Continue until progression / unacceptable toxicity

Criteria

progression on non-steroidal aromatase inhibitor


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Patients with compromised liver or marrow function Doxorubicin

2

20mg/m IV weekly for patients with compromised liver or marrow function due to tumour infiltration


Ensure normal renal function prior to cycle 1 and repeat during subsequent cycles if clinically indicated

•

Patients with abnormal hepatic function should be treated cautiously

•


•


•

FBC prior to each cycle.

•

Normal limits for administration apply with the exception that for patients with marrow infiltration treatment may be continued at lower platelet and neutrophil counts at treating physician discretion.

Continue with weekly treatment usually for 6-8 weeks before changing to fortnightly or 21 day cycles depending on response. Maximum total dose 450mg/m

2

2

Paclitaxel 80mg/m IV weekly for patients with compromised liver or marrow function who have previously received anthracyclines.

Pre-medication Dexamethasone

8mg IV before first cycle 4mg IV before second and subsequent cycles

Chlorphenamine

10mg IV

Ranitidine

50mg IV

Laboratory investigations •


•


•


•


•


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2

Vinorelbine

25 - 30mg/m IV

day 1 and 8 of a 21 day cycle. or

2

60- 80mg/m oral

day 1 and 8 of a 21 day cycle

Repeat at 21 days from day 1

Reassess after every 2 cycles, maximum 6 cycles Criteria: WHO performance status 0-1 Endocrine resistant Prior alkylating agent therapy



•


•


•


Capecitabine

2

1000-1250mg/m oral twice daily for 14 days followed by 7 days off

Or 2

850-1000mg/m twice daily for 14 days followed b y 7 days off if heavily pre-treated or elderly


Repeat at 21 days from day 1 for up to six cycles.

Criteria

Failed or unsuitable for anthracycline and/or taxane PS 0-2



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Bone directed therapy Bisphosphonate Zoledronic acid

4mg IV in 100mls Sodium chloride 0.9% over 15-30 minutes repeated at 28 day intervals.

Criteria:

Performance status 0-2 Symptomatic / extensive bone metastases

Calcium supplements:

Patients should have their serum calcium measured every four weeks and Adcal D3 tablets prescribed as necessary.

Renal impairment Cr clearance

Dose

>60

4.0mg

50 - 60

3.5mg

40 - 49

3.3mg

30 –39

3.0mg

< 30

no treatment

Serum creatinine should be repeated every 4 weeks and if it rises significantly during treatment zoledronic acid should be witheld until the creatinine has returned to within 10% of the baseline prior to starting.

For patients with creatinine clearance < 30ml/min ibandronic acid 50mg weekly oral may be considered.

*This is available via the off-protocol mechanism

*Denosumab

120mg sc monthly

Criteria

Patients ineligible for IV bisphosphonate due to poor venous access or renal impairment


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Management of patients with HER2 positive cancers Trastuzumab

4 mg/kg loading dose IV. over 90 minutes followed by 2mg/kg/week IV over 30 minutes for 8 doses then 6mg/kg every 3 weeks over 30minutes.

or

8mg/kg IV loading dose over 90min then 6mg/kg over 60min for one dose and then over 30 min thereafter if no problems every 3 weeks

Criteria:

Strongly HER2 positive (HER2 3+ by IHC or FISH positive) Trastuzumab given together with a taxane or vinorelbine as first or second line treatment or second / third line as a single agent.

NB not with anthracycline and with care within close proximity to anthracycline therapy (< 6 months).

LVEF: baseline ECHO/MUGA + 3 monthly repeat advised for patients receiving treatment with trastuzumab.

*Lapatinib (Tyverb ®) + capecitabine

Lapatinib 1250mg po daily continuously

+ 2

Capecitabine 1000mg/m oral twice daily for 14 days followed by 7 days off or 2

850mg/m twice daily for 14 days followed by 7 days offif heavily pre-treated or elderly


Repeat at 21 days until progression or toxicity. For some responding patients continuing with lapatinib alone may be the right approach if capecitabine toxicity becomes unacceptable.

Criteria

Prior anthracycline, taxane and trastuzumab PS 0-2 IHC 3+ or FISH positive cancer

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•


•


•


*Available via the Cancer Drug Fund *Paclitaxel Albumin (Abraxane®) 260mg/m2 IV repeat at 21 day intervals

Consider if no longer safe to continue with paclitaxel or docetaxel. Patients may be able to receive Abraxane® with premedication and appropriate precautions.

Criteria Metastatic breast cancer Situations where taxanes are indicated



•


•


•


*Available via the Cancer Drugs Fund

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Gastrointestinal Cancer Oesophageal Carcinoma Adjuvant Not currently recommended as standard therapy

Neoadjuvant Cisplatin/5FU

Cisplatin

80mg/m2 IV

day 1

Fluorouracil

1g/m2 over 24hrs IV

days 1-4

or Capecitabine

1000mg/m2 bd x 14 days

Repeat at 21 days for two cycles.

Criteria

PS 0-1 Cr Cl > 50ml/min Operable oesophageal cancer

Laboratory Investigations 

Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated

•

Calculate creatinine clearance prior to each cycle and administer cisplatin according to guidelines

•


•


•


Locally advanced

Chemo-radiation protocol

Cisplatin/5FU

2

Cisplatin

80mg/m IV day 1 and 29

Fluorouracil

1g/m IV over 24hrs days 1-4 and 29-32

2

or Capecitabine

2

825mg/m oral bd Mon-Fri during XRT

+ XRT followed by two additional cycles after completion of XRT

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•


•


•


•


Cisplat/Capecitabine + XRT (SCOPE trial protocol) 2

Cisplatin 60mg/m IV

day 1

+ 2

Capecitabine 625mg/m oral bd

days 1-21


Repeat at 21 day intervals for 4 cycles with radiotherapy concurrent with cycles 3 and 4



•


•


•


•


Metastatic Cisplatin/5FU

2

Cisplatin

80mg/m IV

Fluorouracil

day 1

2

1g/m IV over 24hrs

days 1-4

or Capecitabine

2

1000mg/m bd x 14 days

Repeat at 21 day intervals, max 4-6 cycles

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Gastric / Adenocarcinomas of Gastro-oesophageal junction Carcinoma Neoadjuvant / Adjuvant For patients with operable cancers after initial staging

ECF/X x 3 cycles

ECF/X



Surgery -- ECF/X x 3 cycles 2

day 1

2

day 1

Epirubicin

50mg/m IV

Cisplatin

60mg/m IV

Fluorouracil

200mg/m / day via continuous IV infusion for 21 days

2

or 2

Capecitabine 625mg/m bd

days 1-21

NB see capecitabine renal function recommendations p130 Repeat at 21 day intervals



•


•


•


•


Adjuvant EOF/X

2

Epirubicin

50mg/m IV

Oxaliplatin

130mg/m IV

Fluorouracil


2

day 1 day 1

2

or Capecitabine 625mg/m2 bd

days 1-21


Repeat at 21 day intervals for a maximum of 6 cycles



•


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•


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Locally advanced / metastatic ECF/X

2

day 1

2

day 1

Epirubicin

50mg/m IV

Cisplatin

60mg/m IV

Fluorouracil


2

or 2


days 1-21


Repeat at 21 day intervals for a maximum of 4-6 cycles

Laboratory investigations Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated •


EOF/X

•


•


•

Normal FBC limits for administration apply 2

Epirubicin

50mg/m IV

Oxaliplatin

130mg/m IV

Fluorouracil


2

day 1 day 1

2

or Capecitabine 625mg/m2 bd

days 1-21



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•


•


•


•


Cisplatin/fluoropyrimidine/Herceptin 2

Cisplatin

80mg/m IV day 1 2

Fluorouracil 1g/m over 24hrs IV days 1-4 or 2

Capecitabine 1000mg/m bd x 14 days


Herceptin

8mg/kg IV day 1 loading dose 6mg/kg IV every 21 days until progression

Criteria

PS 0-1 Cr Cl > 50ml/min HER 2 status IHC 3+ or FISH positive






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


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*Cisplatin/Teysuno 2

Cisplatin

75mg/m IV day 1 2

Teysuno 25mg/m bd po for 21 days

Repeat at 28 day intervals for up to 6 cycles

Criteria

PS 0-1 Cr Cl > 50ml/min Intolerant of capecitabine / 5FU or at high risk of cardiac toxicity















*available via the off protocol mechanism

Second line 2

Irinotecan

250mg/m IV day one of a 21 day cycle repeat x 4 cycles 2

Option to increase to 350mg/m if well tolerated

atropine 600micrograms s/c prior to irinotecan



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•


•


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Pancreatic cancer Adjuvant Fluorouracil+Folinic acid

Fluorouracil 425mg/m2 IV

daily days 1-5

Folinic acid 50mg IV

daily days 1-5

Cycles are repeated at 28 days for 6 cycles.

NB: For patients over 70yrs and those with borderline performance status the dose of Fluorouracil should be reduced to 370mg/m2 per day.



•


•


•


Gemcitabine

1g/m

2

IV weekly for 3 weeks followed by one week break Repeat 28 day cycles for up to 6 cycles.

Criteria

PS 0-2 R0, R1 resection M0



NB: transaminases may rise during gemcitabine therapy •


•


•


Advanced

First line

Gemcitabine + Capecitabine 2

Gemcitabine

1g/m

Capecitabine

825mg/m

IV days 1, 8, 15 2

po bd for 21 days

NB see capecitabine renal function recommendations p130 Repeat 28 day intervals for up to 6 cycles.

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Criteria

PS 0-1





•


•

CA19-9 every 4 weeks

•

Day 8 or 15

9

Platelets 75 – 99 x10 /l 9

Platelets < 75x10 /l

Gemcitabine

1g/m

2

 continue

 omit

at full dose

gemcitabine

IV weekly for 3 weeks followed by one week break Repeat 28 day cycles for up to 6 cycles. or IV weekly for seven weeks followed by one week break for first cycle then 3 weeks on, one off as above.

Criteria

PS 0-2





•


•


•

Day 8 or 15

9

Platelets 75 – 99 x10 /l 9

Platelets < 75x10 /l

 continue

 omit

at full dose

gemcitabine

Second line Ox-Cap

2

Oxaliplatin

85 mg/m IV day 1

Capecitabine

900mg/m oral bd x 9 days

2


Repeat at 14 day intervals for 6 cycles then reassessment

Criteria

PS 0-2 Relapse < 6 months post adjuvant chemotherapy Progression free interval > 3 months following first line therapy

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•


•

FBC and creatinine prior to each cycle

•

Normal FBC limits for administration apply with the exception that the lower limit for 9

platelets for administration of Ox-Cap is 75 x 10 /l

OxMdG

2

Oxaliplatin

85 mg/m IV

Folinic acid

350mg flat dose two hour IV infusion day 1

Fluorouracil

400mg/m 15 minute IV bolus

Fluorouracil

day 1

2

2

2400mg/m 46hr IV infusion start

day 1 day 1


Avoid in patients with pre-existing neuropathy



•


•


•


platelets for administration of OxMdG is 75 x 10 /l

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Cholangiocarcinoma / Gall Bladder Carcinoma Advanced Gemcitabine + Cisplatin Gemcitabine

1000mg/m

Cisplatin

25mg/m

2

2

day 1 and 8

day 1 and 8


Criteria PS 0-1

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Gemcitabine

•


•


•


•


1g/m

2

IV weekly for 3 weeks followed by one week break Repeat 28 day cycles for 4- 6 cycles.

Criteria

PS 0-2



ECF/EOX

•


•


•


•


day 1

2

day 1

Epirubicin

50mg/m IV

Cisplatin

60mg/m IV

Fluorouracil

200mg/m / day via continuous IV infusion

2

or 2

Oxaliplatin

130mg/m IV

Epirubicin

50mg/m IV

2

2


day 1 day 1 days 1-21





•


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•


•


•


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Hepatocellular carcinoma* Sorafenib

Sorafenib Initial dose 200mg bd increasing to 400mg bd over 4 weeks to 400mg bd oral continuously

Continue until disease progression

Criteria

PS

0-2 Normal bilirubin Transaminases < 2xULN Normal renal function


FBC, U/Es, LFTs prior to each cycle

•


•

Discontinue if deteriorating renal or liver function

•


*NB Available via the Cancer Drugs

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Neuroendocrine tumours High mitotic rate, anaplastic histology, clinically aggressive

Etoposide / cisplatin

2

Etoposide

120mg/m IV

Cisplatin

70mg/m IV

2

days 1-3 days 1

Repeat at 21 day intervals max 6 cycles

Criteria

PS 0-1 Cr cl > 50ml/min Patients with rapidly progressive disease



•


•


•


•


Low mitotic rate, well differentiated histology, clinically indolent

Somatostatin short acting analogue titrated to achieve maximum benefit then switch to long acting preparation

Pancreatic neuroendocrine tumours

*Everolimus (Afinitor ®) ®)

10mg oral daily


Ensure normal renal and hepatic function prior to each cycle 1

•


•


•


Criteria

*NB

*Sunitinib (Sutent®) Issue Date:

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•


•


•


Criteria

*NB

No prior anti-VEGF therapy

Available via the Cancer Drugs Fund

Progression Progression on first line therapy

Streptozotocin/Doxorubicin 2

Streptozotocin

500mg/m IV

Doxorubicin

50mg/m

2

days 1-5 repeat every 6 weeks

IV

day 1 repeat every 3 weeks



•


•


•


*Octreotide

Octreotide LAR 20-30mg IM monthly

Criteria non-functioning neuroendocrine tumour of mid gut or uncertain primary origin Locally inoperable or metastatic disease Well differentiated histology


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Colorectal Adjuvant 2

5FU/FA

Fluorouracil 370mg/m IV + folinic acid 50 mg IV weekly x 24 weeks



•


•

FBC prior to every fourth week

•


Capecitabine

2

1250mg/m oral twice daily for 14 days followed by 7 days off 2

Consider 1000mg/m for patients over 70yrs

NB see capecitabine renal function recommendations p130 Repeat at 21 days from day 1 for eight cycles.



•


•


•

Repeat creatinine if clinically indicated

•


XELOX

2

Oxaliplatin

130 mg/m IV day 1

Capecitabine


2



Consider carefully in patients with pre-existing neuropathy

Consider omitting oxaliplatin if persistent neuropathy develops.

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Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated.

OxMdG

•


•


•

Normal FBC limits for administration apply. 2

Oxaliplatin

85 mg/m IV

day 1

Folinic acid


Fluorouracil


Fluorouracil

2400mg/m 46hr IV infusion

2

2

day 1 start day 1


Consider carefully in patients with pre-existing neuropathy

Consider omitting oxaliplatin if persistent neuropathy develops.



•


•


•



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Rectal cancer - Chemoradiation 2

5FU + XRT

Fluorouracil 1000mg/m IV days 1-4 and 22-26 (or final week)

Or

Fluorouracil 300mg/m

2

+ Folinic acid 50mg

IV weekly during the radiotherapy



•


•


•


Capecitabine + XRT

2

Capecitabine 825mg/m oral bd Mon-Fri during XRT




•


•

FBC each week during chemotherapy

•


5FU/FA

Fluorouracil 300mg/m IV + folinic acid 50 mg IV weekly during XRT



Issue Date:

•


•

FBC prior to every fourth week

•


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Advanced Colorectal Cancer First line

Single agent

MdG

MdG:

Folinic acid 350mg flat dose two hour IV infusion day 1 2

Fluorouracil 400mg/m 15 minute IV bolus 2

Fluorouracil 2800mg/m 46hr IV infusion start

day 1 day 1

repeat at 14 day intervals, re-evaluate after 6 cycles.



•


•


•


Capecitabine

2

1250mg/m oral twice daily for 14 da ys 2

Consider 1000mg/m if age >70yrs NB see capecitabine renal function recommendations p130



Ensure normal renal and hepatic function prior to cycle 1 if clinically indicated

•


•


•


Raltitrexed (Tomudex®)

2

3mg/m IV repeat at 21 day intervals for a maximum of 6 cycles

Criteria:

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Patients intolerant of fluoropyrimidines

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Ensure normal renal and hepatic function prior to cycle 1 if clinically indicated

•


•


•


Combination chemotherapy 2

IrinMdG

Irinotecan 180mg/m IV + atropine 600micrograms s/c prior to irinotecan

MdG:

Folinic acid 350mg flat dose two hour IV infusion day 1 2

Fluorouracil 400mg/m 15 minute IV bolus 2

Fluorouracil 2400mg/m 46hr infusion

day 1 start day 1

Repeat at 14 day intervals Review after 12 weeks and consider continuing to 24 weeks if:

•

SD / response.

•

Acceptable toxicity

Criteria: PS 0-2



•


•


•


I-Cap

Irinotecan 180mg/m IV + atropine 600micrograms s/c prior to irinotecan 2

Capecitabine 900mg/m oral bd x 9 days



Review after 12 weeks and consider continuing to 24 weeks if:

•

SD / response.

•

Acceptable toxicity

Criteria: PS 0-1

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OxMdG

•


•


•


Oxaliplatin

85 mg/m IV

day 1

Folinic acid


Fluorouracil


Fluorouracil

2400mg/m 46hr IV infusion

2

2

day 1 start day 1





•


•


•



Ox-Cap

2

Oxaliplatin

85 mg/m IV day 1

Capecitabine


2

NB see capecitabine renal function recommendations p130 Repeat at 14 day intervals for 6 cycles then reassessment




•


•


•



XELOX

Issue Date:

2

Oxaliplatin

130 mg/m IV day 1

Capecitabine


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2

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•


•


•

Normal FBC limits for administration apply.

OxMdG + Cetuximab 2

Oxaliplatin

85 mg/m IV

Folinic acid


Fluorouracil


Fluorouracil

2400mg/m 46hr IV infusion start

Cetuximab

day 1

2

2

day 1 day 1

2

Week 1 500mg/m IV day 1 over 2 hours using 0.2um in-line filter 2

Then 500mg/m IV over 1 hour every 2 weeks

Premedication

Dexamethasone 8mg Chlorphenamine 10mg Ranitidine 150mg




•


•

FBC and biochemistry prior to each cycle

•



Criteria

KRAS wild type cancer PS 0-1 Metastatic disease confined to the liver and potentially resectable if downsized Primary resected or resectable Avoid in patients with pre-existing neuropathy

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IrinMdG + Cetuximab 2

Irinotecan

180mg/m IV + atropine 600micrograms s/c prior to irinotecan

Folinic acid


Fluorouracil

400mg/m 15 minute IV bolus day 1

Fluorouracil

2400mg/m 46hr infusion start day 1

Cetuximab

Week 1 500mg/m IV day 1 over 2 hours using 0.2um in-line filter

2

2

2

2

Then 500mg/m IV over 1 hour every 2 weeks

Premedication

Dexamethasone 8mg Chlorphenamine 10mg Ranitidine 150mg

Repeat at 14 day intervals. Review after 12 weeks and consider continuing to 24 weeks if:

•

SD / response.

•

Acceptable toxicity



•


•


•



Criteria

KRAS wild type cancer PS 0-1 Metastatic disease confined to the liver and potentially resectable if downsized Primary resected or resectable

*Bevacizumab 14 day schedules: 21 day schedules

Criteria

Bevacizumab 5mg/kg IV infusion Bevacizumab 7.5mg/kg IV infusion

Advanced colorectal cancer First line chemotherapy With oxaliplatin or Irinotecan based combination chemotherapy

*NB

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Second / third line chemotherapy

Irinotecan + MdG (see above)

Oxaliplatin + MdG (see above)

I-Cap (see above)

Ox-Cap (see above)

Irinotecan

2

180mg/m IV day 1 of a 14 day cycle atropine 600micrograms s/c prior to irinotecan

or 2

350mg/m IV day one of a 21 day cycle atropine 600micrograms s/c prior to irinotecan



•


•


•


*Bevacizumab

14 day schedules:

Bevacizumab 5mg/kg IV infusion

21 day schedules

Bevacizumab 7.5mg/kg IV infusion

Criteria

Advanced colorectal cancer Second line chemotherapy With oxaliplatin based combination chemotherapy

*NB


*Irinotecan + Cetuximab

Criteria - Must have KRAS wild type cancers - Previously responded to chemotherapy - Second or third line chemotherapy - Performance status (0-1) Issue Date:

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Cetuximab

Irinotecan

2

Week 1

500mg/m IV day 1 over 2 hours using 0.2um in-line filter

Then

500mg/m IV over 1 hour every 2 weeks

2

2

180mg/m IV every 2 weeks + atropine 600micrograms s/c

Premedication Dexamethasone 8mg Chlorphenamine 10mg Ranitidine 150mg


* Available via the Cancer Drug Fund * Cetuximab single agent Criteria - Must have KRAS wild type cancers - Previously responded to chemotherapy - Third line chemotherapy - Performance status (0,1)

Cetuximab

2

Week 1

500mg/m IV day 1 over 2 hours using 0.2um in-line filter

Then

500mg/m IV over 1 hour every 2 weeks

2

Premedication Dexamethasone 8mg Chlorphenamine 10mg Ranitidine 150mg


* Available via the Cancer Drug Fund 2

MMC + MdG

Mitomycin-C 7mg/m IV day 1 repeat every 6 weeks (max 4 doses) + Folinic acid 350mg flat dose two hour infusion 2

Fluorouracil 400mg/m 15 minute IV bolus day 1 2

Fluorouracil 2400mg/m 46hr IV infusion start day 1

Repeated at 14 day intervals

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•


•


•


MMC + Capecitabine Mitomycin-C 7mg/m IV day 1 repeat every 6 weeks, max 4 doses 2

Capecitabine 1000mg/m oral bd for 14 days repeat at 21 day intervals




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•


•


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Anal Carcinoma Localised squamous carcinoma of the anus

Combined XRT + chemotherapy 2

Mitomycin C

12mg/m IV day 1 only (max 20mg)

Fluorouracil

1000mg/m IV over 24hrs days 1-4

Fluorouracil

1000mg/m IV over 24hrs daily x 4 during final week of XRT

2 2

or Capecitabine

2

825mg/m bd oral on each XRT treatment day




•


•


•


Palliative / Metastatic

Cisplatin/5FU

2

Cisplatin

60mg/m IV (max 120mg)

Fluorouracil

1g/m IV over 24hrs

2

day 1 days 1-4

or Capecitabine

2

1000mg/m bd x 14 days

Repeat at 21 day intervals max 4 courses



•


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•


•


•


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Mitomycin C / Fluoropyrimidine 2

Mitomycin C

7mg/m IV day 1 repeat every 6 weeks, max 4 cycles

Fluorouracil

1000mg/m IV over 24hrs days 1-4 repeat at 21 day intervals

2

or Capecitabine

2

1000mg/m bd po days 1-14 repeat at 21 day intervals



Issue Date:

•


•


•


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Gynaecological Cancer Epithelial Ovarian Cancer First Line Chemotherapy

Paclitaxel/Carboplatin Paclitaxel Carboplatin

Paclitaxel premedication

175mg/m2

IV over 3 hours

AUC 5/6

IV over 1 hour

Chlorphenamine

10mg

Dexamethasone

20mg

Ranitidine

50mg

Repeat at 21 day intervals maximum 6 courses

Criteria

Stage Ib-IV

Minimal residual disease / bulk r esidual disease PS 0-1 Cr Cl > 50ml/min



•

Calculate or measure creatinine clearance prior to first cycle and before subsequent cycles if clinically indicated

•


•

CA125 prior to each cycle

•


•


*Paclitaxel/Carboplatin/Bevacizumab 2

Paclitaxel

175mg/m IV over 3 hours

Carboplatin

AUC 5/6 IV over 1 hour

Bevacizumab

7.5mg/kg


Chlorphenamine

10mg

Dexamethasone

20mg

Ranitidine

50mg

Repeat at 21 day intervals maximum 6 cycles chemotherapy max 18 cycles bevacizumab Criteria

Stage III (residual disease >1cm) or IV PS 0-1 Cr Cl > 50ml/min

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•


•


•


•


•


*Available via the cancer drugs Fund

or

Carboplatin

Carboplatin AUC 5/6 x (GFR + 25) IV at 21-28 day intervals x max 6 cycles



•


•


•


•


•


Second line chemotherapy Relapse > 6 months post platinum

Single agent carboplatin Carboplatin AUC 5-6 IV repeated every 28 days x 4-6 cycles



•


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•


•


•


•


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Single agent cisplatin 2

Cisplatin 80mg/m IV repeated every 21 days x 4-6 cycles



•


•


•


•


•


Paclitaxel + carboplatin st

See 1 line section for doses + pre-medication schedule

Repeat at 21 day intervals, max 6 doses



•


•


•


•


•


Carboplatin + Gemcitabine Carboplatin

AUC4 IV at 21 day intervals

Gemcitabine

1000mg/m IV days 1 and 8 of a 21 day cycle

2

Repeat at 21 day intervals to a maximum of 6 cycles •


•


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•


•


•


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Carboplatin + Liposomal Doxorubicin (Caelyx®) Carboplatin

AUC5

Liposomal Doxorubicin (Caelyx®)

30mg/m IV

2

Repeat at 28 day intervals to a maximum of 6 cycles

•


•


•


•


•


•


Single agent Paclitaxel 2

Paclitaxel

70mg/m IV weekly

Pre-medication Dexamethasone

8mg IV before first cycle 4mg IV before second and subsequent cycles

Chlorphenamine

10mg IV

Ranitidine

50mg IV



•


•


•


•


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Second / Third line chemotherapy options 2

Paclitaxel 175mg/m IV over 3hrs or 2

135mg/m IV over 3hrs (depending on PS / prior treatment)

Premedication

Chlorphenamine

10mg IV

Dexamethasone

20mg IV

Ranitidine

50mg IV


Criteria PS 0-1 No prior taxane therapy Previous platinum 2

Liposomal doxorubicin (Caelyx®) 40-45mg/m by IV infusion initially at 1mg/min q 28 days Maximum 6 cycles

Criteria

PS 0-2 Platinum resistant / refractory No evidence of intestinal obstruction



•


•


•


•


Topotecan

1.25mg/m daily IV over 30 minutes for 5 days q 21 days or 2

3mg/m IV weekly on days 1, 8, 15 of a 28 day cycle

Maximum 4 cycles

Criteria

PS 0-2 Platinum resistant / refractory Cr Cl > 40ml/min

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•


•


•

FBC prior to each dose

•


Gemcitabine

1000mg /m IV days 1,8,15 of a 28 day cycle. Criteria

PS 0-2

Platinum resistant / refractory

Reassess after 3 cycles, maximum 6 cycles



•


•


•


•


Etoposide

50mg bd oral x 7days of 21 day cycle max 6 cycles



•


•


•


•


Chlorambucil

10mg daily oral x 14 days of 28 day cycle max 6 cycles



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•


•


•


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Doxorubicin

2

60mg/m IV q21 days, max 6 cycles



Issue Date:

•


•


•


•


•

Consider LV ejection fraction if history of cardiac disease

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Epithelial Ovarian Cancer – Mucinous Histology First line

Carboplatin / Paclitaxel or single agent carboplatin

Platinum refractory 2

Capecitabine 1250mg/m oral twice daily for 14 days NB see capecitabine renal function recommendations p130




•


•


•


Capecitabine should be the treatment of choice where a central line is contra-indicated eg

•

Failed central venous catheterisation

•

Receiving anticoagulants but NB interaction between warfarin and capecitabine 2

I-Cap

Irinotecan 180mg/m IV + atropine 600micrograms s/c prior to irinotecan 2

Capecitabine 900mg/m oral bd x 9 days



Review after 12 weeks and consider continuing to 24 weeks if:

•

SD / response.

•

Acceptable toxicity

Criteria: PS 0-1



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•


•


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•

Ox-Cap


Oxaliplatin

85 mg/m IV day 1

Capecitabine


2


Repeat at 14 day intervals for 6 cycles then re-assessment




•


•


•



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Endometrial Carcinoma Epithelial

Advanced

Doxorubicin/Cisplatin/Paclitaxel Doxorubicin

45mg/m

2

Cisplatin

50mg/m

2

IV

day 1

IV

day 1

Paclitaxel

160mg/m IV

day 2

Premedication

Chlorphenamine

10mg

Dexamethasone

20mg

Ranitidine

50mg

2

Maximum of 6 cycles at 21 day intervals



•


•


•


•


Mixed Mullerian Tumours

Doxorubicin

2

Doxorubicin 75mg/m IV at 21 day intervals x 6 cycles depending on response



•


•


•


•


or 2

Cisplatin Cisplatin 80mg/m IV at 21 day intervals x 6 cycles

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•


•


•


•

Normal FBC limits for administration apply or 2

Doxorubicin/Cisplatin

Doxorubicin 50mg/m IV Cisplatin

2

50mg/m IV

Maximum of 6 cycles at 21 day intervals



•


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Cervical Cancer Adjuvant Not currently recommended as standard therapy

Pre-XRT

BMC

Bleomycin

30,000 iu IV day 1

Mitomycin-C

10mg/m IV cycles 1,3

Cisplatin

50mg/m IV day 1

2 2

Repeat every 14 days for 2-4 cycles



•


•


•


•


Advanced Squamous Carcinoma

Cisplatin / Topotecan Criteria

1.

>6m from completion of chemo-radiation to relapse

2.

no prior radiosensitising cisplatin

3.

PS 0-1 2

Cisplatin

50mg/m IV

day 1

2

Topotecan

0.75mg/m IV

days 1-3




•


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Paclitaxel/Cisplatin 2

Paclitaxel


Cisplatin

50mg/m IV

2


Chlorphenamine

10mg

Dexamethasone

20mg

Ranitidine

50mg


Criteria

1.


2.


3.

PS 0-1



•


•


•


•


Topotecan

Topotecan 1.2mg/m (max 2mg) IV days 1-5


Criteria

1.

PS 0-2

2.

<6 months post chemoradiation

3.

prior radiosensitising cisplatin



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Dose Modification Episode of neutropenic sepsis reduce dose for ensuing cycles by 40% 9

9

Interval neutrophil count 0.5-1.0 x10 /l or platelets 10 – 50 x10 /l 20% reduction 9

9

Interval neutrophil count <0.5x10 /l or platelets <10x10 /l 40% reduction

Advanced Non-squamous carcinoma

Paclitaxel/Cisplatin 2

Paclitaxel


Cisplatin

50mg/m IV

2


Chlorphenamine

10mg IV

Dexamethasone

20mg IV

Ranitidine

50mg IV


Criteria

1.


2.


3.

PS 0-1



•


Paclitaxel

•


•


•


Paclitaxel

135mg/m IV over 3hrs

Premedication

Chlorphenamine

10mg

Dexamethasone

20mg

Ranitidine

50mg


Criteria

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2.

<6 months post chemoradiation

3.

prior radiosensitising cisplatin

30 October 2012


PS 0-2

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•


•


•


Chemo-radiotherapy schedules Criteria

bulky 1B or 2B PS 0-1 Normal liver / renal / haematology

(1)

2

Cisplatin

40mg/m IV (max 70mg) in 1 litre Sodium chloride 0.9% over 60min weekly x max 6

weeks 2

30mg/m if XRT fields large



•


•


•


•


or

(2)

2

Cisplatin

80mg/m IV day 1

Fluorouracil

1g/m

2

IV days 1-4 and 29-32



•


•


•


•


Erythropoietin may be used to maintain haemoglobin levels during combined modality therapy in these patients. Issue Date:

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Carcinoma of the Vulva

Chemoradiation 2

Mitomycin C

12mg/m (max 20mg) IV day 1

Fluorouracil

1000mg/m IV days 1-4 and 29-32

2



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Haematological Malignancies Hodgkins disease Early HD

PET/CT as part of staging

Group I

Involved field XRT

Group II

ABVD x 3 + IF XRT

Group III

Three cycles full dose chemotherapy + IF XRT or 6 cycles full dose chemotherapy + IF XRT if residual abnormality

Advanced HD Stages III / IV or I / II with mediastinal bulk + / - B symptoms

ABVD

2

Doxorubicin

25mg/m IV

day 1 and 15

2

Bleomycin

10000iu/m IV

day 1 and 15

Hydrocortisone

100mg IV

day 1 and 15

Vinblastine

6mg/m IV

Dacarbazine

350mg/m IV

2

day1 and 15 (max 10mg)

2

day 1 and 15

Repeat at 28 day intervals to CR + 2, min 6 max 8 cycles



•


•


•


ChlVPP

Vinblastine 6mg/m IV

days 1 and 8 (max 10mg)

2

Chlorambucil 6mg/m po

days 1-14

Prednisolone 40mg po

days 1-14

Procarbazine 50mg oral tds

days 1-14

Repeat 28 days from day 1 x 6 cycles)

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Non-Hodgkins Lymphoma Low grade First line CVP-R Cyclophosphamide

600mg/m2 IV

day 1

Vincristine

1.4mg/m2 IV

day 1 (maximum 2mg)

Prednisolone

50mg orally

days 1-5

Rituximab

375mg/m2 IV

day 1

Repeat at 21 day intervals to a maximum of 6-8 cycles.



•


•


•


*Bendamustine

2

120mg/m IV days 1 and 2 Repeat at 21 day intervals to a maximum of 8 cycles



•


•


•


*NB available via the Cancer Drug Fund

CHOP-R

2

Cyclophosphamide

750mg/m IV

Doxorubicin

50mg/m IV

Vincristine

1.4mg/m IV

day 1

Prednisolone

50mg po

days 1-5

Rituximab

2

2

2

375mg/m IV

day 1 day 1

day 1


Criteria: fit patients with bulky disease

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•


•


•


*Maintenance Rituximab Rituximab

375mg/m

2

IV every 3 months for 2 years

Criteria CR or PR following first line therapy Must commence within 2 months of completion of first line therapy


Mantle Cell Lymphoma

*Bendamustine

2

120mg/m IV days 1 and 2


Criteria Option for first line therapy



•


•


•


*NB available via the Cancer Drug Fund Second Line

*Bendamustine

2

120mg/m IV days 1 and 2


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•


•


•


Criteria

Unable to receive R-CHOP Unable to receive high dose therapy


Second / third line

Chlorambucil +/- Prednisolone

Chlorambucil

10mg daily orally for 14 days

+ Prednisolone

20mg oral daily for 14 days




Fludarabine

•


•


•


Fludarabine

2

40mg/m orally days 1-5 (only 3 days if heavily pre-treated)


Criteria

Progressed after alkylating agents and anthracyclines Age < 75yrs PS 0-1 Normal marrow function

NB: patients receiving fludarabine should have all blood products Irradiated

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•


•


•


Rituximab

Rituximab 375mg/m

Criteria

2

in 500ml Sodium chloride 0.9% IV weekly x 4

Stage III / IV follicular / Mantle cell NHL Chemoresistant (prior alkylating agent and anthracycline chemotherapy)

Normal renal / hepatic function Anticipated survival > 3 months Age < 65yrs PS 0-2 Not eligible for a clinical trial

Intermediate / High grade

Stage I CHOP x 3 + involved field XRT



•


•


•


Stage II-IV

CHOP-R

2

Cyclophosphamide

750mg/m IV

Doxorubicin

50mg/m IV

Vincristine

1.4mg/m IV

2

2

day 1 day 1 day 1 (max. 1mg if aged >70)

Prednisolone

50mg po

days 1-5

Rituximab

375mg/m IV

2

day 1


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•


•


•


Relapsed Intermediate / High grade A proportion of patients with relapsed intermediate / high grade NHL m ay be salvaged with high dose chemotherapy + marrow / PBSC rescue. Patients in this situation should be discussed with the NHL MDT at the Royal Liverpool Hospital.

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Head and Neck Cancer Locally advanced disease XRT +Cisplatin/5FU

2

Cisplatin

80mg/m IV

day 1

2

Fluorouracil 1g/m over 24hrs IV

days 1-4

Repeat at 21 day intervals for 2-4 cycles prior to XRT



•


•


•


•


or

XRT + Cisplatin

2

Cisplatin

100mg/m IV days 1, 22, and 43 with concomitant XRT



•


•


•


•


or

XRT + Cisplatin / 5FU / Docetaxel 2

Cisplatin

80mg/m IV

day 1

Fluorouracil

1000mg/m over 24hrs IV

Docetaxel

75mg/m IV

2

days 1-4

2

day 1

Repeat at 21 day intervals for 3 cycles prior to CTX/XRT

Criteria

Locally advanced SCC suitable for CTX/XRT PS 0/1 Creatinine clearance > 50mls/min

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•


•


•


•


XRT + Cetuximab 2

Cetuximab

400mg/m IV loading dose 1 week prior to XRT 2

250mg/m IV weekly during XRT

Criteria

Locally advanced SCC suitable for CTX/XRT Unsuitable for cisplatin eg creatinine clearance < 50mls/min PS 0/1



•


•


•


Recurrent or Metastatic Disease

Cisplatin/5FU

2

Cisplatin

80mg/m IV

day 1

Fluorouracil

1g/m IV over 24hrs

2

days 1-4

or

Cisplatin

2

Cisplatin

100mg/m IV




•


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*Cisplatin or Carboplatin + /5FU + Cetuximab

Cisplatin/5FU

2

Cisplatin

80mg/m IV

day 1

5Fluorouracil

1g/m IV over 24hrs

2

days 1-4

Repeat at 21 day intervals max 6 cycles Or

Carboplatin/5FU

Carboplatin

AUC 5

Day 1

Fluorouracil

1g/m IV over 24hrs

2

Days 1-4


Cetuximab

2

400mg/m IV loading dose week 1 2

250mg/m IV weekly during chemotherapy and may be continued until progression

Criteria

Ist line chemotherapy for advanced disease PS 0/1

No prior treatment with cetuximab

Laboratory investigations Ensure normal hepatic function prior to cycle 1 and repeat during

•

subsequent cycles if clinically indicated Calculate creatinine clearance prior to each cycle and administer

•

cisplatin according to guidelines Where renal / hepatic function are abnormal treatment is at physician

•

discretion •


•


*Available via the cancer drugs fund nd

2 Line Chemotherapy for advanced disease 2

Paclitaxel

135-175mg/m IV over 3hrs

Dose depends on PS and extent of prior therapy

Premedication

Chlorphenamine

10mg IV

Dexamethasone

20mg IV

Ranitidine

50mg IV

Repeat at 21 day intervals, max 6 cycles Criteria Issue Date:

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Nasopharyngeal Carcinoma Chemoradiation + Adjuvant Chemotherapy Criteria Nasopharyngeal carcinoma Stage III/IV Creatinine clearance > 50ml/min

Chemoradiation Cisplatin 100mg/m2 days 1, 22, 43 to start prior to XRT



•


•


•


•

Normal FBC limits for administration apply followed by:

Adjuvant chemotherapy Commencing 21 days after 3rd cycle of cisplatin 2

Cisplatin

80mg/m IV

day 1

Fluorouracil

1g.m IV over 24 hrs

2

days 1-4




•


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Thyroid Cancer Medullary Thyroid Cancer

*Vandetanib Continue until disease progression

Criteria PS

0-2

Locally advanced unresectable / metastatic First line



•


•



*NB available via the Cancer Drug

Papillary or Follicular Thyroid Cancer

Sorafenib

400mg bd oral continuously

Continue until disease progression

Criteria PS 0-2 Refractory to radioiodine



•


•


•



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Lung Cancer Small Cell Good PS + Limited stage

Cisplatin/etoposide

2

2

Etoposide 120mg/m IV days 1-3 (or PO 240mg/m days 2-3 in 2 divided doses) 2

Cisplatin 70mg/m IV

days 1


XRT commences with cycle 2



•


•


•


•


Concurrent chemotherapy + XRT Cisplatin + etoposide as above with XRT commencing with cycle 2

Good / Intermediate PS Carboplatin / Etoposide Carboplatin

AUC 5 IV

day 1 2

day 1

2

days 2 and 3

Etoposide

100mg/m IV

Etoposide

200mg/m PO in 2 divided doses

Repeat at 21 day intervals x 4 - 6 cycles



•


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•


Poor PS Many poor PS patients will be too ill potentially to benefit from chemotherapy and symptomatic care will be the most appropriate option. For those judged to be fit enough the following may be considered:

(1) Carboplatin

AUC 4 / 5 IV q 21 days x 4 cycles



•


•


•


•


(2) Etoposide

50mg oral bd x 7 - 10 days repeat at 21 days from day 1max 6 courses



•


•


•


Second Line Chemotherapy

(1) Etoposide

50mg oral bd x 7 - 10 days repeat at 21 21 days from day 1max 6 cycles / progression



•


•


•


(2) Carboplatin

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•


•


•


•


(3) CAV

2

Cyclophosphamide

750mg/m IV

Doxorubicin

50mg/m IV

Vincristine

1.4mg/m IV

2

2

Repeat at 21 days for 4 – 6 cycles



•


•


•


(4) Topotecan 2

2.3mg/m oral daily for 5 days

Repeat at 21 day intervals , maximum 4 cycles

Criteria

PS 0-2 Cr Cl > 40ml/min



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Non-Small Cell Lung Cancer Adjuvant Criteria

Stage 1-3 completely resected PS 0-1

Cisplatin/Vinorelbine

Cisplatin

2

80mg/m IV day 1 2

2

Vinorelbine 25mg/m IV day 1 and 8 or oral 60mg/m day 1 and 8

Repeated at 21 day intervals x 3 cycles



•


•


•


•

Normal FBC limits for administration apply or

Carboplatin/Vinorelbine

Carboplatin AUC x 5 IV 2

2

Vinorelbine 25mg/m IV days 1 and 8 or 60mg/m oral day 1 and 8

21 – 28 day cycle x 3 cycles


Ensure normal hepatic function prior to cucle 1 and repeast during subsequent cycles if clinically indicated.

•


•


•


•


Carboplatin/Vinorelbine (split dose)

Carboplatin AUC x 2.5 IV days 1 and 8 Vinorelbine

25mg/m2 IV days 1 and 8 or 60mg/m2

oral day 1 and 8


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•


•


•


•


Locally advanced 2

Chemotherapy + XRT

Cisplatin 20mg/m IV days 1-4 and 16 - 19 + 2

Vinorelbine 15mg/m IV with XRT fractions 1, 6, 15 and 20 Followed at 4-6 weeks by: Cisplatin 80mg/m

2

Vinorelbine 25mg/m

day 1 2

day 1 and 8


Laboratory investigations 


•


•


•


•


Advanced 2

Cisplatin / Pemetrexed Cisplatin 75mg/m IV 2

Pemetrexed 500mg/m IV

Repeat at 21 day intervals x 4 cycles

•

Vitamin B12 injection IM 1 week prior to start + every 9 weeks until completion

•

Folic acid 400micrograms daily oral during treatment

•

Dexamethasone 4mg bd for 3 days start day before pemetrexed

•

Stop all NSAIDS during chemotherapy

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•


•


•


Cisplatin/Vinorelbine

2

Cisplatin

80mg/m IV day 1 2

2

Vinorelbine 25mg/m IV day 1 and 8 (oral vinorelbine 60mg/m day 1and 8)




•


•


•


•


Gemcitabine/Carboplatin

Carboplatin AUC x 5 IV

day 1

2

Gemcitabine 1250mg/m IV

days 1 and 8



Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated NB: transaminases may rise during treatment

•


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Carboplatin/Vinorelbine

Carboplatin

AUC x 4/5 IV

Vinorelbine

25mg/m IV

day 1

2

days 1 and 8

2

days 1 and 8

Or oral vinorelbine

60mg/m




•


•


•


•


Vinorelbine

25-30mg/m IV days 1 and 8 of a 21 day cycle or 2

60-80mg/m oral days 1 and 8

Max 4 courses

Criteria:

No prior chemotherapy PS 0-2



•


•


•


Gemcitabine

Gemcitabine 1000mg/m IV days 1, 8, 15 of a 28 day cycle


Ensure normal hepatic function prior to cycle 1 and repeat during subsequent cycles if clinically indicated NB: transaminases may rise during treatment

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Gefitinib (Iressa®)

Gefitinib

250mg oral daily

Criteria

Locally advanced / metastatic NSCLC EGFR mutation positive First line

Erlotinib (Tarceva®)

Erlotinib

150mg oral daily

Criteria

EGFR mutation positive First line



•


•


•


Maintenance Pemetrexed Maintenance pemetrexed is available through the normal funding mechanism for patients who fulfil the criteria set out by NICE and who did not receive pemetrexed as part of first line therapy. For those patients who received pemetrexed as part of first line therapy and who fulfil the criteria funding is available via the CDF

Pemetrexed

500mg/m2 IV

Repeat at 21 day intervals until progression

•


•


•


•


Criteria: Non-squamous carcinomas PS 0-1 CR/PR/SD following first line chemotherapy First line CTX with Platinum + vinorelbine/paclitaxel/gemcitabine/docetaxel

*Pemetrexed

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Repeat at 21 day intervals until progression •

Vitamin B12 1mg injection IM 1 week prior to start + every 9 weeks until completion

•


•


•


Criteria: Non-squamous carcinomas PS 0-1 CR/PR/SD following first line chemotherapy First line chemotherapy with Cisplatin + Pemetrexed


Second line Chemotherapy

Docetaxel

75mg/m

2

IV q 21 day cycle x max 4 cycles

Dexamethasone 8mg bd x 3 days start 24hrs pre-docetaxel

Criteria

PS 0-1 Previous response or stable disease to platinum based chemotherapy Progression free interval following platinum based chemotherapy > 6m

Laboratory Investigations Ensure normal renal and hepatic function prior to cycle 1 and repeat during

•

subsequent cycles if clinically indicated •


•


•


Erlotinib (Tarceva®)

Erlotinib

150mg oral daily initially for 4 weeks and continued thereafter if symptomatic or objective response

Criteria

Issue Date:

-

Progression following chemotherapy for advanced disease

-

Fit to receive docetaxel as second line therapy

-

No prior anti EGFR therapy

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•


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Mesothelioma 2

Cisplatin / Pemetrexed Cisplatin 75mg/m IV 2



•


•


•

Dexamethasone 4mg bd for 5 days, start day before pemetrexed

•




•


•


•


Carboplatin / Pemetrexed

Carboplatin AUC 4/5 2



•


•


•


•




•


•


•


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Melanoma Advanced

Dacarbazine

2

850mg/m IV q 21 days max 6 cycles



•


•


•


Gemcitabine + treosulphan 2

Gemcitabine 1000mg/m IV days 1 and 8 2

Treosulphan 3500mg/m IV days 1 and 8




•


•


•


*Ipilimumab

3mg/kg IV over 90min



*Vemurafenib

960mg bd until progression

Criteria

Tumour contains BRAF 600 mutation Unresectable or metastatic disease


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Sarcomas Soft Tissue Sarcoma Adjuvant There is no proven role for adjuvant chemotherapy for soft tissue sarcomas. However treatment may be considered when chemo-sensitive tumours such as rhabdomyosarcoma, synovial sarcoma are resected with close margins.

Neo-adjuvant Suggested protocol for down sizing prior to surgery

Doxorubicin

20mg/m2

day 1,2,3

Mesna prior to ifosfamide

3g/m2

day 1,2,3

Ifosfamide + Mesna

3g/m2 / 3g/m2 day 1,2,3

Mesna post ifos/mesna infusion 3g/m2

day 1,2,3

Advanced There is no evidence that combinations are superior to single agents as palliative chemotherapy

First line Doxorubicin

Doxorubicin

2

75mg/m IV q 21 days x 6 cycles



•


•


•


Second line Ifosfamide

2


3g/m days 1,2,3

Ifosfamide/Mesna

3g/m days 1,2,3

Mesna post ifos/mesna infusion

3g/m days 1,2,3

2 2




•


•


•


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2

Dacarbazine 800mg/m IV day 1




•


•


•


*Trabectedin Consider in select cases of advanced STS- Failure after treatment with anthracyclines and ifosfamide or intolerant/contraindications to anthracyclines and ifosfamide. Consider in Myxoid liposarcomas and leiomyosarcomas. PS 0-2 2

1.5 mg/m as IV infusion over 24 hours every 21 days.

*NB Available via the off-protocol mechanism

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Osteosarcoma / MFH of bone / Leiomyosarcoma of Bone

Neoadjuvant / Post operative schedule

PAM x 2 -> Surgery (week 10) -> PAM x 2 -> Doxorubicin - Methotrexate x 2

PAM

2

day 1, 2

2

days 1, 2, 3

Cisplatin

60mg/m IV

Doxorubicin

25mg/m IV

Methotrexate

2

12g/m IV

days 22 and 29

Folinic acid rescue •

Start 24 hrs post start of Methotrexate infusion with 30mg IV 6 hourly

•

Switch to oral after 6 doses if not vomiting

•

Methotrexate levels at 24, 48, 72 hrs etc.

•

Continue until Methotrexate undetectable ie <0.1M usually 4-5 days

Methotrexate level

Folinic acid dose 6hrly

< 0.1M

Stop rescue

<0.5-5M

15-30mg 6hrly

5-50M

200mg/m 6hrly

>50M

1000mg/m 6hrly

2

2

In addition patients urinary pH should be >7 prior to starting Methotrexate infusion

NB: do not give methotrexate if renal function is abnormal or in the presence of a third space. Also avoid all non-steroidal anti-inflammatory agents prior to treatment and until Methotrexate undetectable.

Doxorubicin /Methotrexate 2

Doxorubicin

37.5mg/m IV

Methotrexate

12g/m IV

2

days 1, 2 days 15 and 22

Folinic acid rescue – see above

Criteria

Age < 40yrs PS 0-2

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Cisplatin/Doxorubicin Cisplatin

2

100mg/m IV day 1 2

2

Doxorubicin 25mg/m IV days 1, 2, 3 (20mg/m days 1-3 age > 60yrs)

Repeat at 21 days x 3 cycles then surgery then 3 further cycles.

Criteria

Not suitable for PAM schedule. PS 0-2



•


•


•


•


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Advanced Osteosarcoma 2

Cisplatin/Doxorubicin Cisplatin

100mg/m IV

day 1

2

Doxorubicin 25mg/m IV

days 1, 2, 3

Repeat at 21 days x 6 cycles



•


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•


•


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Ewings Sarcoma Non-metastatic Ewings Sarcoma/PNET/Askin tumour / Rhabdomyosarcoma Laboratory Investigations FBC/Biochemistry/Ca/Mg/Cl/HCO3 each cycle Early morning urine PO4, Creatinine, osmolarity at baseline and repeat every other cycle of VIDE Echo/MUGA baseline/cycle 4 if indicated/cycle 6/ end Rx / pregnant Bone scan/CT chest/MRI primary/Marrow biopsy at baseline MRI primary after cycles 2, 4, 6(omit after 2 if good response)

Neoadjuvant VIDE (cycles 1-6) 2

Vincristine

1.5mg/m (max 2mg) IV day 1

Doxorubicin

20mg/m IV

2

days 1-3

2

Mesna

1g/m

day 1

Etoposide

150mg/m IV

Ifosfamide/Mesna

1.5g/m / 1.5g/m IV

Mesna

1.5g/m IV

2

2

days 1-3 2

2

Pegfilgrastim

days 1-3 days 3

6mg subcutaneous injection

day 4

Evaluation after cycle 4: •

If surgical resection likely proceed to cycles 5 and 6

•

If radiotherapy to be definitive local therapy proceed to cycles 5 and 6

•

If disease progression discontinue and consider surgery or radiotherapy

•

If pre-surgery XRT planned proceed to cycles 5 and 6 omitting doxorubicin

Dose modifications

Haematological toxicity Delayed recovery of wbc / platelets > 6 days reduce etoposide 20% Neutropenic sepsis grade 3 or 4 reduce etoposide 20% Further episodes – repeat etoposide 20% reductions

GI / Mucositis Graded 3 or 4 reduce etoposide by 20%

Cardiac function LVEF < 40% omit doxorubicin and substitute Dactinomycin1.5mg/m

2

Repeat echo after next cycle and consider reintroducing doxorubicin if LVEF has recovered.

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Definitive local treatment •

Surgery should occur 21 days after cycle 6 or as soon as recovery allows.

•

Radiotherapy should commence concurrent with cycle 7 omitting Dactinomycin from concurrent cycles.

•

If radiation is required following surgery it should commence after cycle 8 omitting Dactinomycin from concurrent cycles. 2

VIA (cycles 7-14) Vincristine

1.5mg/m (max 2mg) IV 2

Dactinomycin

0.75mg/m (max 1.5mg)IV


1g/m

Ifosfamide/Mesna

1.5g/m / 1.5g/m IV

2

days 1-2 days 1-2

2

Mesna post ifos/m esna infusion 1.5g/m

day 1

2

2

days 1-2 days 1-2

NB: omit Dactinomycin during radiotherapy

Haematological toxicity Delayed recovery of wbc/platelets > 6 days reduce Dactinomycin & Ifosfamide by 20% Neutropenic sepsis grade 3 /4 reduce Dactinomycin & Ifosfamide by 20% + add GCSF Further episodes should be managed with serial 20% reductions

GI / Mucositis Grade 3 or 4 reduce Ifosfamide + Dactinomycin by 20%

Renal Toxicity GFR > 60 no change GFR 40-59 reduce Ifosfamide by 30%, reduce etoposide by 30% 2

GFR < 40 switch Ifosfamide to cyclophosphamide 1500mg/m on day 1 only reduce etoposide by 30%

Cardiac function LVEF < 40% or 10% decrease from previous level, delay chemotherapy and repeat in 7 days. If recovered proceed with chemotherapy. If still impaired consider omission or dose reduction of Ifosfamide.

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VAC

2

Vincristine

1.5mg/m IV (max 2mg)

day 1

Dactinomycin

0.75mg/m IV (max 1.5mg)

2

day 1-2

2

day 1

Mesna prior to cyclophosphamide 500mg /m IV pre –cyclophosphamide Cyclophosphamide/Mesna

2

2

1500mg/m / 1500mg/m IV

day 1

2

Mesna post cyclo/mesna infusion 1500mg/m IV post cyclophosphamide/mesna day 1

Repeat at 21 days for 4 – 6 cycles



•


•


•


VACA (In patients unsuitable for VIDE previously NOT exposed to anthracyclines. Dactinomycin and doxorubicin on alternate cycles)

2

Vincristine


day 1

2

Mesna prior to cyclophosphamide 500mg /m IV Cyclophosphamide/Mesna

day 1

2

2

1200mg/m / 1200mg/m IV 2

Mesna post cyclos/mesna infusion 1200mg/m IV

day 1

2

Dactinomycin

day 1


days 1-3

Alternating with 2

Doxorubicin

20mg/m IV

days 1-3

Etopside / Ifosfamide Etoposide

120mg/m2 IV

days 1-3


500mg/m2

days 1-3

Ifosfamide/Mesna

3g/m2 / 3g/m2 IV

days 1-3

Mesna post ifos/mesna infusion 1.5g/m2 IV

days 1-3



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•


•


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Palliative Ewings Etoposide / cisplatin Etoposide

2

120mg/m IV

days 1-3

2

Cisplatin

50mg/m IV

days 1-2

Carboplatin

AUC 5 IV

day 1

Etoposide

120mg/m IV

Etoposide

240mg/m PO

or 2

day1

2

days 2,3


Criteria

PS 0-1 Cr cl > 50ml/min for cisplatin



•


•


•


•


Cyclophosphamide/ Topotecan Relapsed Ewing’s sarcoma nd

Relapsed/ 2 line rhabdomyosarcoma Topotecan 0.75 mg/m

2

Days 1-5

Cyclophosphamide 250 mg/m

2

Days 1-5

Cycle repeated every 21 days

Gemcitabine/Docetaxel Relapsed metastatic osteosarcoma rd

Selected metastatic soft tissue sarcomas (3 line)/ uterine leiomyosarcoma nd

Relapsed Ewings (if other 2 line is not suitable)

Day 1

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675 mg/m

2

IV over 90 minutes

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Day 8

Gemcitabine

675 mg/m2 IV over 90 minutes followed by

Docetaxel

75-100mg/m2 IV over 60 minutes

Dexamethasone 8 mg bd for 3 days to start 24 hours pre docetaxel (ie Days 7-9)

Cycle repeated every 21 days

Irinotecan/Temozolomide Relapsed Ewing’s sarcoma Relapsed/ 2nd line rhabdomyosarcoma

Irinotecan 20 mg/m2 IV

Days 1-5, Days 8-12

Temozolomide 100mg/m2 po

Days 1-5

Cycle repeated every 21-28 days

Paclitaxel Angiosarcomas (2nd line or 1st line if not suitable for doxorubicin) 2

80 mg/m weekly up to 12 weeks 2

175 mg/m every 21 days (4-6 cycles, review after cycle 3)

Oral Etoposide Palliative metastatic Ewings or rhabdomyosarcoma

Etoposide 50-100mg bd 7-14 days (at clinician’s discretion)

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Aggressive fibromatosis st

1 Line Tamoxifen +/- NSAID’s nd

2 Line 2

Methotrexate 30 mg/m (usually 50mg total dose) Vinblastine

6 mg/m

2

(usually 10mg total dose)

Every 1-2 weeks Duration of course at clinician’s discretion

Vinorelbine can replace vinblastine if neuropathy is a problem.

Rhabdomyosarcoma Baseline investigations:

-

FBC, U+E’s, LFT’s Bone chemistry

-

CT thorax / Abdo staging

-

Bone marrow aspirate and trephine

-

Bone Scan

-

If paramningeal site- CSF

-

Consider early morning urine for phosphate, creatinine, osmolarity for Ifosfamide containing regimes

For patients aged < 40 years: IVADo regime for high risk rhabdomyosarcoma (see separate regime)

Maintenance therapy: 2

Vinorelbine 25 mg/m IV D 1, 8, 15 2

Cyclophosphamide 25 mg/m PO OD D 1-28 Every 28 days

Maintenance therapy following IVADo to be used in:

1.

For Alveolar Rhabdomyosarcoma maintenance therapy following IVADo for 6 cycles ( i.e. 6 months)

2.

For metastatic disease on intensive treatment, if no residual disease or limited residual disease, IVADo to be followed by maintenance treatment for 12 cycles

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For patients > 40 years: IVAD Vincristine 1.4 mg/m2 (max dose 2mg) D1 Doxorubicin 30 mg/m2 D1, D2 2

Mesna 1.2g/m pre ifosfamide D1,D2 2

Ifosfamide 3g/m D1,D2 2

Mesna 2.4g/m post ifosfamide in 2 divided doses D1,D2


VAC Vincristine Dactinomycin

2


Day 1

2

0.75mg/m IV (max 1.5mg)

Day 1 and 2

2

Mesna prior to cyclophosphamide 500mg /m IV pre –cyclophosphamide Cyclophosphamide/Mesna

2

Day 1

2

1500mg/m / 1500mg/m IV

Day 1

2

Mesna post cyclo/mesna infusion 1500mg/m IV post cyclophosphamide/mesna

Day 1


IVA Vincristine

1.5mg/m2 (max dose 2mg)

Day 1

Dactinomycin

1.5 mg/m2 (max single dose 2mg)

Day 1


1.2g/m day

Ifosfamide/Mesna

3 g/m / 3 g/m2

2

Days 1-2

2

Days 1-2

2

Mesna post ifos/mesna infusion 2.4g/m split into 2 doses

Day 2


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IVADo Regime for High Risk Rhabdomyosarcoma Cycle 1

Cycle 2

Cycle 3

Cycle 4

Surgery/

Week

IVADo

V

V

IVADo

V

V

IVADo

1

2

3

4

5

6

7

Cycle

Cycle

5

8

15

Cycle

17

18

Cycle

8

IVA

16

Radiotherapy

10

7

IVA 14

9

Cycle

6

IVA

IVADo

9

IVA

Week

13

19

20

I=

Mesna prior to ifosfamide 1.2g/m over 1 hour

21

22

IVA 23

24

25

2

2

2

Ifosfamide/Mesna 3g/ m / 3g/m over 3 hours

Days 1-2

2

Mesna post ifos/mesna infusion 2.4g/m over 8 hours (split into 2 doses) 2

V=

Vincristine 1.5mg/m (max single dose 2mg)

A=

Dactinomycin 1.5 mg/m (max single dose 2mg)

Do=

Doxorubicin 30 mg/m

Day 1

2

Day 1

2

Days 1-2 for cycles 1-4

Each cycle: WCC>2 Neutrophils> 1.0 ( or physician’s discretion) Platelets > 80 Weekly vincristine to be given irrespective of pancytopenia unless unwell rd

nd

Reassess after cycle 3. If not CR or PR > 1/3 consider 2 line treatment + RT

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PAM Chemotherapy for Resectable Osteosarcoma

Cycle 1 AP 1

2

3

Cycle 2

M

M

AP

4

5

6

7

8

SURGERY

M

M

9

10

Cycle 3 AP

11

12

13

14

M

M

15

16

Week Cycle 4 AP 17

18

19

Cycle 5 M

M

A

20

21

22

23

Cycle 6

M

M

A

24

25

26

27

M

M

28

29

Week

AP -

Doxorubicin 25 mg/m2

Days 1-3

Cisplatin 60mg/m2

Days 1-2

M-

Methotrexate 12 g/m2 (With folinic acid rescue) Day 1

A-

Doxorubicin 37.5 mg/m

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2

Days 1-2

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Gastro-intestinal Stromal Tumours (GIST) *Adjuvant

Imatinib po 400mg daily for 36 months

Criteria

Tumour

> 5cm

Mitoses

> 5 mitoses/50 HPF

SI / colonic primary


Imatinib (Glivec®)

Imatinib 400mg daily orally until progression

Criteria

PS 0-2

c-Kit positive locally advanced / metastatic disease



•


•

FBC / biochemistry prior to each visit

•


•

Dose reduce if significant toxicity / rising hepatic transaminases

Sunitinib (Sutent®)*

Criteria

Sunitinib

50mg orally daily for 4 weeks followed by a two week break

PS 0-2 c-Kit positive locally advanced / metastatic disease previous response to imatinib



•


•

FBC / biochemistry prior to each visit

•


*Available via the off protocol mechanism

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Urological Cancer Bladder Cancer - Transitional cell Neoadjuvant Cisplatin/Gemcitabine Cisplatin

2

70mg/m IV

Gemcitabine

1g /m

2

day 1

IV

days 1, 8, 15

Repeat at 28 day intervals for 3 cycles prior to cystectomy



•


•


•


•


Cisplatin / Gemcitabine split dose Cisplatin Gemcitabine

35mg/m

2

1000mg/m

2

IV days

1 and 8

IV days

1 and 8

Repeated on a 21 day schedule for up to 4 cycles

•


•


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•


•


•


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Concurrent Cisplatin / XRT Cisplatin/XRT

2

Cisplatin

30-40mg/m IV weekly x 4-6 weeks as an outpatient (max 60mg) IV over 1 hour

XRT 55Gy in 20# (4 x weekly cisplatin infusions) or XRT 64Gy in 32# (6 x weekly cisplatin infusions)

Criteria

PS 0-1 Poorly differentiated TCC bladder pT2-4a, N0, M0



•


•


•


•


5FU + Mitomycin C/XRT Fluorouracil

500mg/m2

days 1-5 and 16-20 of concurrent XRT

Mitomycin C

12mg/m2

day 1 of concurrent XRT

Criteria

impaired renal function



•


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•


•


•


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Advanced Cisplatin/Gemcitabine 2

Cisplatin

70mg/m IV day 1

Gemcitabine

1g /m

2

IV

days 1, 8

Repeat at 21 day intervals for up to 6 cycles.



•


•


•


•


Cisplatin / Gemcitabine split dose Cisplatin Gemcitabine

35mg/m

2

1000mg/m

2

IV days

1 and 8

IV days

1 and 8

Repeated on a 21 day schedule for up to 4 cycles •


•


•


•


•


Carboplatin/Gemcitabine Carboplatin

AUC4 / 5 IV

Gemcitabine

1g /m



2

day 1

IV

days 1, 8 of a 21 day cycle

For patients with impaired renal function

Repeat at 21/28 day intervals for up to 6 cycles.

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Laboratory Investigation •


•


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•


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Renal cancer Advanced

First line

Interferon

Alpha Interferon

Week 1

by s/c injection:

Mon 5million units Wed 5million units Fri 10million units

Weeks 2+

Criteria

10million units Mon / Wed / Fri

PS 0-1 Relapse post nephrectomy > 12 months Low volume disease Patients should have 2 out of 3 criteria



•


•


•


Sunitinib (Sutent®)

Sunitinib 50mg daily x 4 weeks followed by 2 week break

6 week cycles repeated until progression

Criteria

PS 0-1



Pazopanib

•


•


•


Pazopanib 800mg daily Criteria

First line advanced disease No prior cytokine therapy

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Sorafenib

•


•


•


Sorafenib 400mg bd orally continuously until progression

Criteria

PS 0-1 Progression on/following cytokine therapy



•


•


•


*Temsirolimus

Temsirolimus 25mg IV weekly

Premedication

Chlorphenamine 10mg



•


•


•


Criteria

First line therapy Poor risk patients

*NB

Only available via the Cancer Drug Fund

*Everolimus (Afinitor®) Everolimus10mg oral daily

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•


•


•


Criteria

Second line therapy Biopsy proven RCC Must have had prior VEGF inhibitor

*NB

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Only available via the Cancer Drug Fund

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Prostate Cancer 2

Mitoxantrone

Mitoxantrone 12mg/m IV (max 20mg) q 21 days Maximum total dose 140mg/m

Criteria

2

Endocrine refractory disease PS 0-1 Normal FBC, renal, liver function No cardiac failure



Docetaxel

•


•


•


Docetaxel

75mg/m

IV q21 days

Prednisolone

10mg daily until completion of chemotherapy

Dexamethasone

8mg bd x 3 days start 24hrs pre-docetaxel

Reassessment after two cycles and continue to a maximum of 10 only if responding or stable disease.

Criteria: WHO Performance Status 0-1 Hormone resistant



Abiraterone

•


•


•


Abiraterone 1000mg oral daily Prednisolone 10mg daily until completion of chemotherapy

Criteria

Castrate resistant Prior docetaxel chemotherapy

*Abiraterone Issue Date:

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Prednisolone 10mg daily until completion of chemotherapy

Criteria

Castrate resistant No prior chemotherapy for advanced disease PS 0-1


*Cabazitaxel

2

Cabazitaxel

25mg/m IV infusion.

Prednisolone

10mg daily until completion of chemotherapy

premedication

Chlorphenamine 10mg Dexamethasone 16mg Ranitidine

50mg


Criteria

nd

2 line following docetaxel PS 0-2






•





*NB

Issue Date:

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Germ Cell Tumours Adjuvant Stage I Pure Seminoma

Carboplatin

AUC x 7 IV - one dose only

Carboplatin


EDTA clearance required to calculate AUC

•

Ensure normal hepatic function prior to treatment

•


Stage I Non-seminomatous testicular GCT

Criteria: vascular or lymphatic invasion

BEP3

Bleomycin

30000iu IV

Etoposide

165mg/m IV

Cisplatin

50mg/m IV

day 1, 8, 15

2

days 1-3

2

days 1-2




•


•


•

Tumour markers: HCG,AFP,LDH where appropriate prior to each cycle

•


•


Low risk – all GCT

BEP3

Bleomycin

30000iu IV

day 1, 8, 15

2

Etoposide

165mg/m IV

Cisplatin

50mg/m IV

days 1-3

2

days 1-2

Repeat at 21 day intervals for 3 cycles.

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•


•


•


•


•


Intermediate / High risk – all GCT

BEP5

Bleomycin

30000iu IV

Etoposide

100mg/m IV

Cisplatin

20mg/m IV

days 1, 5, 15

2

cycles 1-3

days 1-5

2

days 1-5

Repeat at 21 day intervals x 3 cycles then EP 5 for a further 3 cycles (i.e. omit bleomycin)



•


•


•


•


•


CNS disease

POMB / ACE + Intrathecal (IT) Methotrexate

POMB

Day 1

Vincristine

2mg IV

Methotrexate

1g/m IV over 24hrs (Standard dose is 300mg/m )

Folinic acid

15mg 6hrly x 12 doses start 12 hrs after completion of

Day 2

Bleomycin

15mg IV over 24hr

Day 3

Bleomycin

15mgIV over 24 hr

Day 4

Cisplatin

120mg/m IV over 12hr

2

2

Methotrexate

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•


ACE

•


•


•


•


Dactinomycin

0.5mg IV

days 1-3

Etoposide

100mg/m IV

Cyclophosphamide

500mg/m

2

Intrathecal (IT) Methotrexate

2

days 1-3

IV

day 3

12.5mg flat dose (folinic acid rescue 15mg 6hrly x 4 start at 24hrs)

Laboratory Investigations Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent

•

cycles if clinically indicated •


•


•


Repeat cycles at 14 days from day 1, POMB, POMB, ACE, POMB, ACE etc 4-5 cycles of POMB.

Initial organ failure 2

Low dose cisplatin / etoposide

Cisplatin 20mg/m IV 2

Etoposide 100mg/m IV Repeat daily x 2-3days depending on clinical situation



•


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•


•


•


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Relapsed NSGCT

TIP

2

Paclitaxel

175mg/m IV 3hr infusion day 1

Ifosfamide

1000mg/m (+mesna) IV days 1-5

Cisplatin

20mg/m IV

2

days 1-5

Premedication

Chlorphenamine

10mg IV

Dexamethasone

20mg IV

Ranitidine

50mg IV

2

Repeat at 21 day intervals x 4 cycles



•


•


•


•


•


High dose chemotherapy May be curative in selected patients with drug sensitive relapsed disease.

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Primary CNS Malignancy Glioblastoma Multiforme – concomitant Temozolomide + XRT 2

Temozolomide

75mg/m oral daily day 1 to completion of XRT

Dose 1 hour pre-XRT and in am at weekends

Co-trimoxazole 960mg oral daily Mon / Wed / Fri until lymphocyte count normal after completing XRT

Laboratory investigations Ensure normal renal and hepatic function prior to cycle 1 and repeat during subsequent cycles if

•

clinically indicated •


•

FBC weekly

if neutrophils < 1.5 or Platelets < 100

Withhold Temozolomide until neuts > 1.5 and platelets > 100

If neutrophils < 0.5 or platelets < 10 stop Temozolomide

Criteria

Age 18 – 70 PS 0 – 1 Absence of HIV, chronic hepatitis B and hepatitis C

Adjuvant Temozolomide 2

days 1-5 cycle 1

2

days 1-5 cycle 2-6 if nadir neutrophil count > 1.5 on cycle 1

Temozolomide 150mg/m oral 200mg/m oral



•


•


•


•

If at any time neutrophil recovery is delayed by > 21 days treatment is discontinued

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Astrocytoma

First line

Lomustine (CCNU) 40mg oral daily days 1-4 Repeat at 4-6 week intervals until progression / unacceptable toxicity



•


•


•


Second line (1)

Temozolomide

2

Temozolomide 150mg/m oral daily for 5 days 2

Escalate to 200mg/m /day for 5 days depending on toxicity

Repeat at 28 day intervals maximum 6 cycles

Criteria: PS 0-3 Glioblastoma multiforme / anaplastic astrocytoma Prior nitrosourea Adequate marrow reserve (plts >100 neut > 1.5) No prior Temozolomide



•


•


•


Third line options

(1)

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50mg oral bd for 14 days q 21-28 days

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•


•


•


(2) Procarbazine

100-150mg/m /day oral days 1-14 repeated every 28 days



•


•


•


Oligodendroglioma / mixed tumours

First line

PCV

Procarbazine

2

60mg/m oral 2

Lomustine (CCNU) 110mg/m oral

day 1

2

Vincristine

days 8-21

1.4mg/m (max 2mg) IV

day 8 and 29

Repeat on a 6 week schedule



•


•


•


Second line

Consider radiotherapy

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Third line 2

Temozolomide






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Primary CNS Lymphoma De Angelis

Weeks 1, 5, 9

Day -1-7 allopurinol 300mg/day

Vincristine

1.4mg/m (max 2mg) IV bolus weeks 2,

Methotrexate


(Modified) 2

2

With adequate folinic acid rescue (see below) and urinary alkalinisation 2

Procarbazine

100mg/m oral daily for 7 days

Weeks 3, 7 2

Vincristine

1.4mg/m (max 2mg) IV bolus weeks 2,

Methotrexate


2

With adequate folinic acid rescue (see below) and urinary alkalinisation

Dexamethasone

16mg/day week 1 12mg / day week 2 8mg/day week 3 6mg/day week 4 4mg/day week 5 2mg/day week 6

Folinic acid rescue

Issue Date:

•

Start 24 hrs post start of Methotrexate infusion with 30mg IV 6 hourly

•

Switch to oral after 6 doses if not vomiting

•

Methotrexate levels at 24, 48, 72 hrs etc.

•

Continue until Methotrexate undetectable ie <0.1M usually 4-5 days

Methotrexate level

Folinic acid dose 6hrly

< 0.1M

Stop rescue

<0.5-5M

15-30mg 6hrly

5-50M

200mg/m 6hrly

>50M

1000mg/m 6hrly

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In addition patients urinary pH should be >7 prior to starting Methotrexate infusion

NB: do not give methotrexate if renal function is abnormal or in the presence of a third space. Also avoid all non-steroidal anti-inflammatory agents prior to Rx and until Methotrexate undetectable.



•

Calculate creatinine clearance prior to each cycle and administer methotrexate only if clearance is > 50mls/min

•


•


•


Medulloblastoma (adult) Relapse following surgery / XRT

First line PCV

2

Procarbazine

60mg/m oral

Lomustine

110mg/m oral

Vincristine

1.4mg/m (max 2mg) IV day 8 and 29

2

days 8-21 day 1

2

Repeat on a 6 week schedule



•


•


•


Second line

Temozolomide

2




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Adenocarcinoma of Unknown Primary Origin Possible GI primary

MdG / capecitabine / gemcitabine

Possible breast primary Manage as for similar stage breast cancer

Possible ovarian primary Carboplatin 5 x (GFR+25)

Possible lung primary

Carboplatin / Gemcitabine

Midline nodal disease

+/- lung metastases

BEP3 x max 4 cycles depending on response

Undifferentiated carcinoma

Etoposide / platinum 2

2

Etoposide

120mg/m days 1-3 (or oral 240mg/m )

Cisplatin

70mg/m days 1

2




•


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CCC Emergency Chemotherapy Drugs Likely cancers requiring treatment: •

Lymphoma

•

Germ Cell Tumours

•

Small Cell Lung Cancer

Drugs Available Cisplatin

30mg in 250ml Sodium chloride 0.9% x 2 doses

Etoposide

100mg x 2 doses

Doxorubicin

50mg

Cyclophosphamide

800mg

Vincristine

2mg

Pegfilgrastim

6mg

These drugs will be stored in oncology pharmacy in the fridge in the dispensary area labelled Fridge 3. The fridge will be labelled as containing Emergency Chemotherapy Drugs. Cisplatin will be stored at room temperature on top of fridge 3.

Emergency chemotherapy should be prescribed by a consultant and entry to the pharmacy will be via the CCC bleep holder only.

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Bone Metastases There is increasing evidence from studies in a number of malignancies that intravenous bisphosphonate therapy can ameliorate bone pain and reduce the risk of skeletal complications in patients with bone metastases. At present for suitable patients the recommended treatment is zelodronate + Adcal D3 until progression.

Bisphosphonates

Zoledronic acid 4mg IV in 100mls Sodium chloride 0.9% over 15-30 minutes repeated at 28 day intervals.

Criteria:

Performance status 0-2 Symptomatic / extensive bone metastases

Calcium supplements: Patients should have their serum calcium measured every four weeks and Adcal D3 prescribed as necessary.

Renal impairment:

Cr clearance

Dose of zoledronic acid

(Cockcroft-Gault) >60

4.0mg

50 - 60

3.5mg

40 - 49

3.3mg

30 –39

3.0mg

< 30

no treatment

Serum creatinine should be repeated every 4 weeks and if it rises significantly during treatment zoledronic acid should be witheld until the creatinine has returned to within 10% of the baseline prior to starting.

Ibandronate (Bondranat®) Bondranat has yet to be shown to be as effective as zoledronic acid in reducing the incidence of skeletal events and thus we cannot recommend it as routine treatment. However for patients who have difficulties with venous access or renal impairment it may be requested via the off protocol mechanism.

*Denosumab

Denosumab 120mg sc monthly

Criteria

Patients ineligible for IV bisphosphonate due to poor venous access or renal impairment

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CCC anti-emetic guidelines for cytotoxic chemotherapy •

Oral And IV anti-emetic formulations have equivalent efficacy

CCC Classification of chemotherapy by emetic potential (updated February 2012) LEVEL AGENT High Emetic Risk Cisplatin ≥ 50mg/m² (>90 % frequency of Cyclophosphamide > 1500mg/m² emesis) Dacarbazine Procarbazine (oral) Streptozocin AC Combination defined as either doxorubicin or epirubicin with cyclophosphamide 2 Doxorubicin >60mg/m 2 Epirubicin >90ml/m 2 Ifosfamide > 10g/m 2

Moderate Emetic Risk (30-90 % frequency of emesis)

Bendamustine Carboplatin Cisplatin < 50mg/m² Cyclophosphamide ≤1500mg/m² Cyclophosphamide (oral) Dactinomycin 2 Doxorubicin <60mg/m 2 Epirubicin <90mg/m Etoposide (oral)

Ifosfamide <10g/m Interferon alpha >10million international 2 units/m Irinotecan Lomustine Melphalan >50mg/m² Methotrexate> 250 mg/m² Oxaliplatin Temozolomide (oral) Vinorelbine (oral)

Low Emetic Risk (10-30 % frequency of emesis)

Cabazetaxel Capecitabine Docetaxel Doxorubicin (Liposomal) Eribulin Etoposide (IV) Evorolimus Fludarabine (oral) Fluorouracil Gemcitabine

Interferon alpha >5 <10million 2 international units/m Methotrexate >50mg/m² < 250mg/m² Mitomycin Mitoxantrone Nilotinib Paclitaxel Paclitaxel-albumin (Abraxane) Pemetrexed Sunitinib Topotecan Vandetanib

Minimal Emetic Risk (<10 % frequency of emesis)

Alemtuzumab Alpha Interferon Bevacizumab Bleomycin Cetuximab Chlorambucil (oral) Erlotinib Fludarabine Gefitinib Imatinib (oral) Interferon alpha <5million 2 international units/m Ipilimumab Lapatinib

Melphalan (oral low-dose) Methotrexate ≤ 50mg/m² Pazopanib Panitumumab Rituximab Sorafenib Rituxumab Temsirolimus Trastuzumab Vinblastine Vincristine Vinorelbine (IV)

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Emetic Risk HIGH– CISPLATIN REGIMENS Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 + Dexamethasone 12mg PO/IV day 1then 4mg BD PO days 2-4 (as TTH) + Ondansetron 24mg PO or 12mg IV (maximum 32mg) day 1 + Domperidone 10-20mg four times a day as required HIGH – NOT CONTAINING CISPLATIN Dexamethasone 12mg IV/oral PO/IV day 1 then 4mg BD PO days 2-4 (as TTH) + Ondansetron 24mg PO or 12mg IVday 1, then 8mg twice a day PO days 2-4 (as TTH) + Domperidone 10-20mg four times a day as required

Second Line

Antiemetic Failure

Ondansetron 8mg + dexamethasone 8mg + Lorazepam 1mg by

Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthrough nausea and vomiting Treat on subsequent courses of chemotherapy with second line agents

IV infusion over 24 hours

Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 + Dexamethasone 12mg PO/IV day 1then 4mg twice a day PO days 2-4 (as TTH) + Ondansetron 24mg PO or 12mg IV (maximum 32mg) day 1

Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthrough nausea and vomiting Treat on subsequent courses of chemotherapy as for second line

Aprepitant 125mg PO day 1, 80mg PO daily days 2-3 + Dexamethasone 12mg PO or IV days 1-4 + Ondansetron 16-24mg PO or 8-12mg IV (maximum 32mg) day 1

Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthrough nausea and vomiting Treat on subsequent courses of chemotherapy as for high risk

MODERATE Dexamethasone 8mg PO/IV day 1 then 4mg twice a day PO days 2-4 (as TTH) + Ondansetron 16mg PO or 8mg IV (maximum 32mg/day) day 1 + Domperidone 10-20mg four times a day as required LOW Dexamethasone 8 mg PO or IV day 1 + Domperidone 10-20mg four times a day as required

Ensure antiemetics have been taken regularly. Commence on first line antiemetics for breakthrough nausea and vomiting Treat on subsequent courses of chemotherapy as for moderate risk

MINIMAL Routine prophylaxis not always required. Domperidone 10-20mg four times a day as required

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ALTERNATIVES/BREAKTHROUGH Cyclizine 50mg three times a day is often used for protracted nausea Prochlorperazine 5-10mg oral three times a day Prochlorperazine Suppositories 25mg three times a day Metoclopramide 10-20mg four times a day Levomepromazine 6mg at night (this can be increased to 12mg)

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GCSF Primary Prophylaxis Patients receiving FEC/Docetaxel adjuvant chemotherapy for breast cancer, EC/AC neoadjuvant chemotherapy for breast cancer and VIDE for STS have a high risk of neutropenic events and in line with ASCO guidelines we recommend primary prophylaxis with pegfilgrastim 6mg 24hrs post chemotherapy.

Secondary Prophylaxis In other situations where the risk of neutropenic events is lower we do not routinely recommend primary prophylaxis with GCSF and CCC policy is that secondary prophylaxis is reserved for the following situations:

(1) To maintain dose intensity in potentially curable malignancies where the dose limiting toxicity is neutropenia eg

-

Germ cell tumours

-

Intermediate / high grade lymphomas

-

Hodgkins disease

-

Sarcomas prior to potentially curative surgery

-

Adjuvant chemotherapy

Thus if chemotherapy is delayed due to a neutropenic episode defined as either:

•

9

Infection associated with neutropenia (neutrophil count < 1.0x10 /l)

or

•

9

9

Total wbc < 3.0x10 /l and neutrophil count < 1.0 x10 /l on the day the chemotherapy cycle was due.

Then prophylaxis with pegfilgrastim 6mg s/c administered 24hrs post chemotherapy.

(2) Infection associated with protracted neutropenia > 7 days

There is no evidence that giving GCSF to patients with neutropenic sepsis improves outcomes in terms of survival or reduced incidence of medical sequelae. However for febrile patients with neutropenia lasting more than 7 days GCSF may be considered.

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Palliative Chemotherapy Patients who are receiving palliative chemotherapy should be managed with appropriate dose reductions if problems with neutropenia arise.

Prophylactic antibiotics The use of prophylactic antibiotics following cyctotoxic chemotherapy can result in a small reduction in febrile episodes but at the expense of side effects and the potential risk of inducing antibiotic resistance and increasing the risk of clostridium difficile infection. The use of prophylactic antibiotics is not therefore recommended routinely but should be reserved for patients thought to be at particularly high risk of infection. The current CCC protocol is:

Ciprofloxacin 500mg oral BD days 9 – 20 post chemotherapy dependent on nadir

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Erythropoietin Erythropoietin may be used to maintain haemoglobin levels during chemotherapy in patients where transfusion is contra-indicated e.g.

•

Religious grounds

•

Cardiac failure

In addition erythrpoietin may be considered in patients who have required two or more transfusions and who are due to receive further chemotherapy.

Erythropoietin may also be used to maintain haemoglobin levels during combined modality therapy for cervical cancer.

Protocol Hb > 12

no treatment required

Hb < 12

darbepoetin 150micrograms / sc weekly

If Hb rises to > 14 stop until Hb < 12 then restart at 100micrograms / week

If Hb rises by > 2g/dl / month reduce dose to 100micrograms / week

If Hb does not rise after 4 weeks treatment increase to 300micrograms / week

If no response after a further weeks then stop treatment.

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Intrathecal (IT) Chemotherapy Department of Health regulations now dictate that intra-thecal chemotherapy may only be prepared and administered by specific named individuals.

•

Prescriptions must be written on the intra-thecal prescription form

•

Patients must receive any IV chemotherapy prior to IT treatment

•

The doctor administering the IT drugs must collect them in person from pharmacy.

•

The drugs must be checked by the doctor and a qualified chemotherapy nurse prior to administration

•

All staff members involved (doctor, nurse, pharmacist) must be on the current IT chemotherapy register.

Methotrexate is the only drug we use as intrathecal therapy at a flat dose of 12.5mg.

Cytosine, thiotepa and hydrocortisone may also be given intrathecally.

All other chemotherapy drugs are potentially lethal when adm inistered intrathecally

In addition any diluent used to prepare an intrathecal drug must be aqueous based and not alcohol based.

Intrathecal chemotherapy must always be given under the direction of a consultant and administered by one of the doctors on the CCC approved list.

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Creatinine Clearance Wright Creatinine Clearance Formula Women

((6580 – (38.8 x age)) x bsa x 0.832) /creatinine

Men

((6580 – (38.8 x age)) x bsa ) /creatinine

NB

Weight in kg Creatinine in umol/l

Calvert formula for Carboplatin dosage Carboplatin dose in mg = AUC x (Creatinine clearance + 25)

Desired area under the curve (AUC) normally 4-6 depending on protocol and clinical situation

Cisplatin dose guidelines Cisplatin is nephrotoxic and thus patients must have their renal function measured prior to each cycle.

Creatinine clearance

Cisplatin dose

> 50mls /min

100%

40 – 50 mls / min

75%

< 40mls / min

no further cisplatin

•

Patients should only commence cisplatin chemotherapy if they have an adequate performance status ie 0-2. The only exception to this is patients with advanced germ cell tumours with poor PS who may commence treatment with low dose etoposide / platinum.

•

Patients should only receive second and subsequent cycles of cisplatin if they are well and have suffered no deterioration in performance status.

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Cisplatin Hydration Policy Cisplatin doses 20 – 40mg/m2 (Outpatients) Cisplatin in 1000mL Sodium Chloride 0.9%

IV over 1 hour

Cisplatin doses 20 – 40mg/m2 (Inpatients) Prehydration

Post-hydration

Sodium Chloride 0.9% 500mL Monitor urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 500mL

IV over 1 hour IV over 1 hour IV over 1 hour

Cisplatin doses 41 - 80mg/m2 (Inpatients/Daycase)

Prehydration

Post-hydration

Furosemide Sodium Chloride 0.9% 1000mL (+ 20mmol Potassium Chloride) Monitor Urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 1000mL (+ 20mmol Potassium Chloride )

PO 20mg IV over 90 minutes

IV over 90 minutes IV over 90 minutes

Cisplatin doses >81mg/m2 (Inpatients)

Prehydration

Post-hydration

Furosemide Sodium Chloride 0.9% 1000mL (+ 20mmol Potassium Chloride) Monitor Urine Output Cisplatin in 1000mL Sodium Chloride 0.9% Sodium Chloride 0.9% 1000mL (+ 20mmol Potassium Chloride) Sodium Chloride 0.9% 1000mL

PO 20mg IV over 2 hour

IV over 4 hours IV over 4 hour IV over 4 hour

n.b. Where Urine Output is of concern, please contact a clinician for advice.

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Haematological Indices – Guidelines for the administration of chemotherapy (1) 9

administer

9

administer

Platelets > 100x10 /l + Total WBC > 3 x10 /l + 9

Neutrophils >1.0x10 /l

administer

(2) 9

Platelets <100x10 /l

physician discretion

or 9


9


Total WBC < 2.9 x10 /l or Neutrophils < 1.0x10 /l

•

These guidelines assume that patients are well with good performance status, that other acute toxicities have resolved and the patient has not had a previous episode of neutropenic sepsis.

•

In some situations chemotherapy is given despite lower blood count values than those noted above. These include patients receiving adjuvant chemotherapy, those with curable metastatic malignancies such as germ cell tumours and lymphomas and also patients with bone marrow infiltration. These situations will be dealt with on a c ase by case basis.

Capecitabine-Renal function recommendations Prior to starting treatment:

CrCl > 50

full dose

CrCl 30 – 49 75% dose

CrCl <30

omit

During treatment if there was a rise in serum creatinine the CrCl should be re-calculated and further treatment adjusted according to the above

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Neutropenic Sepsis Policy 9

Patients admitted with a fever associated with neutropenia (N < 1x10 /l) are scored according to the presence or absence of risk factors.

Age

Dehydrated requiring iv fluids

Hypotensive

Presence of COPD

Symptoms related to infection

> 60yrs

=0

< 60

=2

No

=3

Yes

=0

Systolic <90

=0

>90

=5

Yes

=0

No

=4

None

=5

Mild

=5

Moderate

=3

Severe

=0

Was the patient already in hospital Yes No

Score

=0 =3

17 + = low risk <17= high risk

Low risk: Co-amoxiclav 625mg tds + ciprofloxaxin 750mg bd or

Oral doxycycline 200mg bd + ciprofloxaxin 750mg bd If penicillin allergy or Ceftazidime iv 1g bolus then 2g / 24 hours continuous infusion If unable to take oral medication or already on antibiotics at home or Ceftazidime iv 1g bolus then 2g / 24 hours continuous infusion + vancomycin If evidence of central line infection

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High risk: Gentamicin + piperacillin/tazobactam (Tazocin) 4.5g tds

Gentamicin + iv ciprofloxacin 400mg bd if penicillin allergy

Add vancomycin if central line infection suspected

Other pathogens Anaerobic infection suspected: metronidazole 500mgtds

Atypical respiratory infection suspected: Clarithromycin 500mg bd

Platelet Transfusion Policy Platelets required if: 9

Platelets < 10x10 /l 9

Platelets < 100x10 /l and significant bleeding

Hypocalcaemia Calcium gluconate 10% 10mls given by slow IV injection tds then orally if needed ECG and calcium monitoring required

Hypomagnesaemia Patients who present with symptoms suggestive of hypomagnesaemia Patients who have previously had hypomagnesaemia and who are due to have further platinum chemotherapy.

Symptomatic patients with Mg <0.5 or <0.4 regardless of symptoms.

Consider urgent replacement if Mg <0.4 and cardiac history (IHD, AF, AVF……).

If normal renal function: 40 mmol in 250 mls Sodium chloride 0.9% over 2 hours.

If suspected abnormal renal function (Cr >125umol/l) or already an inpatient: 40 mmol in 1L Sodium chloride 0.9% over 8 hours.

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Re-check Mg if symptoms persist or if indicated for other reasons

Do not give more than 40 mmol in one day.

Ifosfamide Encephalopathy and Methylene Blue Most mild cases of ifosfamide encephalopathy will spontaneously resolve within 24-72 hours. However, consider use of methylene blue if Grade 3/ Grade 4 neurotoxicity (i.e. somnolence >30% of time, disorientation/ hallucination/ echolalia/ perseveration/ coma, or seizures on which consciousness is altered, or which are prolonged, repetitive or difficult to control).

Methylene Blue 50mg IV every 6 hours.

For future infusions, methylene blue 50 mg prior to infusion of ifosfamide and 50mg every 6 hours during infusion

Ifosfamide Renal Toxicity Pre-treatment: Serum

Na, K, Ca, PO4, Cl, total CO2/HCO3, AP

Early morning urine

PO4 Creatinine, Osmolarity

Tp/Creat = PO4 serum – PO4 urine x Creat serum umol/l Creat urine

GFR

Tp/Creat

HCO3

Action

> 60

>1.0

>17.0

Ifosfamide 100%

40-59

0.8-0.99

14.0-16.9

Ifosfamide 70%

< 40

<0.8

>14.0

Switch to cyclophosphamide 1500mg/m2 IV Day 1

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Folinic acid rescue for High Dose Methotrexate Time after starting methotrexate

24 HRS

48 hrs

Methotrexate Plasma concentration in micromol/L If serum creatinine is greater that 50% of normal limit, double the folinic Acid dose Start folinic acid 15mg/m2 IV every 6 hours, then follow table below < 0.1M

0.5 – 5M

5 – 50M

Stop rescue

15mg-30mg

200mg/m

6 hourly 72 hrs

Stop rescue

15mg-30mg 6 hourly

96 hrs

Stop rescue

15mg-30mg 6 hourly

120 hrs

Stop rescue

>50M 2

6 hourly 200mg/m

2

6 hourly 200mg/m

2

6 hourly

15mg-30mg

200mg/m

6 hourly

6 hourly

2

1000mg/m

2

6 hourly 1000mg/m

2

6 hourly 1000mg/m

2

6 hourly 1000mg/m

2

6 hourly

CCC Dose Banding Policy Rationale It is widely recognised that using body surface areas (BSA) is not the most accurate method of calculating chemotherapy doses. Dose banding does not result in a significant dose variation from the traditional method as the maximum variation between the standard dose and the dose comprising each band is 5% or less. A range of pre-filled syringes may be used to administer the dose. This system has worked successfully in Cancer Centres in the UK

1, 2

.

For all intravenous chemotherapy agents there is a threshold below which it is not possible for pharmacy to guarantee the accuracy of a given dose. This usually corresponds to approximately 5% of a standard dose e.g. 10mg of Docetaxel.

Given that the calculation of chemotherapy doses on the basis of surface area is at best an educated guess, treatment is unlikely to be compromised by rounding the dose to the nearest 5% increment.

Oral agents have to be dose rounded often to a much larger tolerance e.g. Etoposide 10-16%.

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ranges or bands are rounded up or down to predetermined standard doses. The initial step is to decide on the bands and how best to arrive there from the calculated dose. Taking BSA to 2 decimal place and rounding the dose to the nearest 1ml volume (taking concentration into account) appears to be the simplest way forward. All cytotoxic doses are rounded up/down, which allows easier manipulation within pharmacy.

For the following drugs the doses prescribed should be rounded or banded to the indicated pharmacy tolerance level. For drugs not on this list clinicians should round the dose to the nearest figure that approximates to 5% of the total dose.

Drugs dispensed at CCC

Dactinomycin (Actinomycin-D) Doses rounded to nearest 0.1mg dose 6

Aldesleukin (Proleukin) 18 *10 IU /1ml 6

Doses rounded to nearest 1MU (*10 ) dose

Alemtuzumab (30mg/1ml Vial) Used for TBI patients at CCC – Usual dose 10mg

Bevacizumab (400mg /16ml and 100mg / 4ml) Doses rounded to nearest 25mg dose

Bleomycin (15000 IU Vial) Usual dose either 15,000IU or 30,000IU

Liposomal Doxorubicin (Caelyx®) 20mg /10ml Liposomal Doxorubicin 45mg/m2 (Do not dose band trials)

BSA

1.3 -1.49

60mg

1.5- 1.69

70mg

1.7-1.89

80mg

>1.9

90mg

Calcium Folinate 300mg /30ml vial Folinic acid syringes for 5FU/FA regime dispensed as 50mg flat dose DeGramont type regimes dose dispensed at 350mg flat dose

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Cetuximab (100mg /50ml Vial) Doses rounded to nearest 2mg dose

CMF Regimes 2

BSA (m ) < 1.39 1.40 - 1.59 1.60 -1.74 1.75 - 1.84 > 1.85

5FU Dose 800mg 900mg 1000mg 1100mg 1200mg

Methotrexate Dose 55mg 60mg 65mg 70mg 80mg

Cyclophosphamide Dose 50mg TDS14/7 50mg TDS 14/7 50mg TDS 14/7 50mg TDS 14/7 50mg QDS 14/7

If Cyclophosphamide 50mg BD 14/7 or 50mg QDS 14/7 required, Dr to specify on script.

Cisplatin (100mg /100ml) Doses rounded to nearest 10mg dose

Cyclophosphamide (1gram Vial) Doses rounded to nearest 20mg dose

Doses >800mg should be rounded to the nearest 100mg dose.

Dacarbazine (1gram Vial) Doses >1000mg should be rounded to the nearest 100mg dose.

Docetaxel (80mg Vial) 2

2

BSA (m ) 1.40 – 1.59

Docetaxel Dose (100mg/m ) 150mg

1.60 –1.79

170mg

1.80 – 2.00

190mg

Doxorubicin (200mg / 100ml Vial) Doses should be rounded to nearest 2mg dose

Doses > 80mg should be supplied in presentations corresponding to the nearest 10mg

Etoposide (500mg /25ml) Doses rounded to nearest 20mg dose

Etopophos® (Etoposide Phosphate) 100mg Vial Doses rounded to nearest 10mg dose

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Epirubicin 50mg/m

2

DOSE (mg) 70 80 90 100

1.54 – 1.69 1.70 – 1.89 >1.90

Epirubicin 100mg/m

2

DOSE (mg) 1.31 –1.34 1.35 – 1.44 1.45 – 1.54 1.55 – 1.64 1.65 – 1.74 1.75 – 1.84 1.85 –1.92 >1.93

130 140 150 160 170 180 190 200

Epirubicin and Doxorubicin doses > 80mg should be dose banded to the nearest 10mg dose

Epirubicin and Doxorubicin doses < 80mg should be rounded to nearest 2mg dose

Fluorouracil (500mg / 100ml Vial)

Doses < 1000mg should be rounded to nearest 50mg dose Fluorouracil doses >1000mg should be rounded to the nearest 100mg dose.

Fluorouracil LV5 Pumps For DeGramont type regimes should be banded as below:

2400mg/m

2

BSA 1.45 – 1.51 1.52 – 1.61 1.62 – 1.71 1.72 – 1.82 1.83 – 1.92 >1.93 2800mg/m

Dose 3500mg 3750mg 4000mg 4250mg 4500mg 4750mg

2

BSA 1.45 – 1.47 1.48 – 1.56 1.57 – 1.65 1.66 – 1.72 1.73 – 1.86 1.87 – 2.00 Issue Date:

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Fluorouracil doses at 1000mg /m

2

BSA 1.26 – 1.35 1.36 – 1.45 1.46 – 1.55 1.56 – 1.65 1.66 – 1.75 1.76 – 1.85 1.86 – 1.95 >1.96

Dose 1300mg 1400mg 1500mg 1600mg 1700mg 1800mg 1900mg 2000mg

Gemcitabine (1gram Vial) Doses dispensed to nearest 38mg dose 2

2

BSA (m )

Gemcitabine Dose (1000 mg/m )

1.40 – 1.49

1400mg

1.50 –1.69

1600mg

1.70 – 1.89

1800mg

1.90 – 2.00

2000mg

2

2

BSA (m )

Gemcitabine Dose (1250 mg/m )

1.40 – 1.49

1800mg

1.50 –1.69

2000mg

1.70 – 1.89

2300mg

1.90 – 2.00

2500mg

Irinotecan (100mg / 5ml) 2

2

BSA (m ) 1.40 – 1.59

Irinotecan Dose (180mg/m ) 260mg

1.60 –1.79

300mg

1.80 – 2.00

340mg

Ifosfamide (2gram Vial) Doses rounded to nearest 80mg dose

Methotrexate (500mg / 20ml) Doses rounded to nearest 5mg dose

Mesna (1000mg / 10ml) Doses rounded to nearest 100mg dose

Mitomycin (10mg Vial) Doses rounded to nearest 1mg dose

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Mitoxantrone (20mg /10 ml) Doses rounded to nearest 2mg dose

Oxaliplatin (100mg and 50mg Vial) 2

2

BSA (m ) 1.40 – 1.59

Oxaliplatin Dose (85mg/m ) 130mg

1.60 –1.79

150mg

1.80 – 2.00

170mg

Paclitaxel (300mg / 50m, 100mg / 16.7ml, 30mg / 5ml) Doses < 230mg rounded to nearest 6mg dose 2

Paclitaxel 175mg/m should be banded to the strengths below: BSA 1.30 – 1.34 1.35 – 1.42 1.43 – 1.46 1.47 – 1.62 1.63 – 1.79 1.80 – 1.94 1.94 – 2.00

Dose 230mg 240mg 250mg 270mg 300mg 330mg 350mg

Pemetrexed (500mg / 20ml) Doses rounded to nearest 50mg dose

Rituximab (100mg and 500mg Vial) Doses rounded to nearest 10mg dose

Topotecan (4mg Vial) Doses rounded to nearest 0.1mg dose

Trastuzumab (150mg Vial) Doses rounded to nearest 21mg dose

Treosulfan (1gram and 5 gram Vial) Doses rounded to nearest 100mg dose

Vinblastine (10mg / 10ml Vial) Doses rounded to nearest 1mg dose

Vincristine ( 2mg / 2ml) Doses rounded to nearest 0.1mg dose

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Vindesine (5mg /5ml) Doses rounded to nearest 1mg dose

Vinorelbine (50mg / 5ml) Doses rounded to nearest 5mg dose as below

2

BSA (m ) 1.25 to 1.34 1.35 to 1.44 1.45 to 1.54 1.55 to 1.64 1.65 to 1.74 1.75 to 1.84 1.85 to 1.94 1.95

IV dose 2 25 mg/m Dose (mg) 30 30 35 40 40 45 45 50

Oral dose 2 60 mg/m Dose (mg) 80 80 90 100 100 110 110 120

IV dose 2 30 mg/m Dose (mg) 40 45 50 50 55 55 55 60

Oral dose 2 80 mg/m Dose (mg) 100 110 120 130 140 140 150 160

Oral Vinorelbine is available in 20mg and 30mg Capsules

25mg IV Vinorelbine = 60mg Oral Vinorelbine dose 30mg IV Vinorelbine = 80mg Oral Vinorelbine dose

The dose of oral Vinorelbine is approx 2.5 times that of IV Vinorelbine

References

1.

Plumridge R, Sewell G. Dose banding of cytotoxic drugs: A new concept in cancer chemotherapy. Am J Health Syst Pharm 2001; 58: 1760 –4.

2.

Baker J P, Jones S E. Rationalisation of chemotherapy services at the University Hospital Birmingham NHS Trust. J Oncol Pharm Prac 1998; 4: 10 –14.

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30 October 2012


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