North Wales Cancer Network

The editor has compiled this formulary as a list of treatment regimens, which are intended to be a guide to baseline chemotherapy only. It is neither a legal nor a prescriptive document and should not be utilised in anyway as a formal guide to prescribing.

Author: / North Wales Cancer Network
Editor: / Tracy Parry, Lead Network Pharmacist
Version: / 2.1
Approved by: / C&D NHS Trust D&T, NEWT D&T, NWWT D&T committees
Date approved:
Review date: / March 2010

North Wales Cancer Network

Chemotherapy Protocols -2008/9

INTRODUCTION 4

Breast Cancer 6

Oesophageal and Oesophago-gastric CANCER 37

PANCREATIC CANCER 48

Anal Cancer 50

colorectal cancer 52

Ovarian Cancer 68

Endometrial Cancer 75

Cervical Cancer 79

Small Cell Lung Cancer 82

Non-small Cell Lung Cancer 85

Mesothelioma Chemotherapy Regimens 90

Head and Neck Cancer 93

BLADDER CANCER 101

renal cancer 104

Prostate Cancer 105

TESTICULAR CANCER 110

mALIGNANT MELANOMA 115

APPENDIX I 122

Preparation of a clinical case 122

Pharmacy Assessment 122

Capacity Assessment (Day Treatment Unit) 122

Presentation to the Network Formulary Group 123

Commissioning assessment 123

Further work 123

D+T committees 124

Other Trust Committees 124

Appeal Mechanism 124

Table 1 Membership of Network Formulary Group 124

APPENDIX II 129

APPENDIX III 130

APPENDIX IV 131

APPENDIX VII 134

Highly emetogenic regimens 134

Moderately emetogenic regimens 134

Low emetogenic regimens 134

Delayed Emesis 134

Emesis Leading to Admission 134

Anticipatory Emesis 135

APPENDIX VIII 137

INTRODUCTION

This list of protocols for the drug treatment of cancer has been compiled, with the active contribution of the oncology clinicians and the lead oncology pharmacists in the three trusts in North Wales, with the aim of:

· Identifying the core regimen used for the most common forms of cancer

· Informing Trusts and commissioners of the baseline utilisation of chemotherapy

· Acting as an agreed dispensing formulary for pharmacists in terms of the diseases and application of drugs therein

· Providing uniform access to cancer treatment for patients across North Wales.

This list contains the regimens, which are available for use during the year beginning April 1st 2008 to March 31st 2009.

The formulary largely concentrates on regimens used as first and second line. The formulary recognises that third line or individualised use of chemotherapy is more difficult to standardise and this therefore is not included.

Future inclusions

It is hoped that future versions will include sections on:

· Haemato-oncology chemotherapy

· Treatment and prophylaxis of neutropenic sepsis

· Use of blood products

· Use of growth factors

· Extravasation policy

New drugs

The formulary will be reviewed annually .The North Wales Cancer Network formulary group will oversee the revision and implementation of the formulary across North Wales. New submissions to the formulary will be scrutinised by the group following the process in Appendix I.

Inevitable situations will arrive that are not covered by the standard North Wales Cancer network regimens. These may include expensive drugs or combinations prior to a NICE appraisal or not in the NICE or AWMSG appraisal programme.

Consultants who wish to use a non-protocol regimen should apply to their local Drugs and Therapeutic Committee for clinical approval. Once achieved they should then refer to their Directorate or Division to achieve funding.

If funding is unavailable within the Directorate or Division then a submission can be made to individual commissioners but should emanate from the Directorate or Divisional leads not the individual clinician.

Resource Issues.

All the regimens within this formulary should be funded and this includes all NICE drugs approved up to the point of publication March 2008.

However though all the regimens are funded and therefore available it cannot be automatically assumed that all the regimens can be delivered. Clinicians are advised that they must ensure that the regimen in question is deliverable within the identified clinical environment before they offer it to the patient.

In light of this both clinicians and managers are advised to use this formulary as a basis for identifying which chemotherapy regimen should be available to patients in North Wales. In doing so, these regimens should be available in all three Trusts assuming clinical governance and capacity parameters are met.

Breast Cancer

Neo-adjuvant

EC/DOCETAXEL

Patient group: Standard 1st line regimen.

If complete clinical response to four cycles of EC – then 6 cycles of EC in total and no docetaxel.

Chemotherapy: EC x 4 cycles followed by docetaxel x 4 cycles

Patient Group: For patients with locally advanced disease, or to allow less radical surgery in patients with operable tumours.

If limited response after 2 to 3 cycles, consider switching to docetaxel

Chemotherapy: Epirubicin 75mg/m2 i.v. bolus over 3-5 minutes Day 1

Cyclophosphamide 600mg/m2 i.v. bolus over 3-5 minutes Day 1

Repeated at 21 day intervals for 4-6 cycles

Anti-emetics: High emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle

· LV ejection fraction prior to first cycle if patient has history of cardiac problems. Risk of cardiomyopathy increases with cumulative epirubicin dose of > 900mg/m2

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion.

Dose Modifications:

· Epirubicin - Moderate liver impairment (bilirubin: 1.4-3 mg/100ml) give 50% of the dose, severe impairment (bilirubin> 3 mg/100 ml) give 25% of the dose.

Additional Information: Red discolouration of urine may occur for 1-2 days after administration.

DOCETAXEL

Pre-medication: Dexamethasone 8mg po twice daily for 3 days starting the day before treatment. Required for all cycles.

Chemotherapy: Docetaxel 100mg/m2 i.v. infusion over 60 mins Day 1

Repeat every 21 days for 4 cycles

Additional

Medication: Prophylactic ciprofloxacin 500mg po twice daily for 7 days starting on days 5

Anti-emetic: Moderate emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle.

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion.

Dose modification:

· Neutrophils < 1.0 x 109/L defer dose

Platelets < 100 x 109/L defer dose

AST or ALT > 1.5 x upper limit normal reduce dose by 25%

> 3.5 x upper limit normal discontinue

· Non-haematological toxicities (excluding alopecia):if necessary delay treatment by one or more weeks until recovery to grade 0 or 1; if recovery takes longer than one week or if toxicity of grade 3+ is documented during chemotherapy, the dose should be reduced by 20% in all subsequent cycles.

· Docetaxel: If ALT/AST > 1.5 x ULN and ALP 2.5 x ULN give 75% of dose. If bilirubin > 22μmol/L +/- ALT/AST> 3.5 x ULN with ALP > 6 x ULN contraindicated.

1. P Piedbois et al Annals of Oncology 2007 18(1):52-57

2. von Minckwitz G, Raab G, Caputo A, et al. (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23:2676–2685
Adjuvant

EPI-CMF (E-CMF)

Patient group: Epi-CMF is standard for all breast patients except node positive tumours who are offered FEC/Docetaxel

Chemotherapy: Epirubicin 100mg/m2 i.v. bolus over 3-5 minutes Day 1

Repeated at 21 day intervals for 4 cycles

Followed by CMF 4 cycles (Classical Bonnadonna)

Anti-emetic: High emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle

· LV ejection fraction prior to first cycle if patient has history of cardiac problems. Risk of cardiomyopathy increases with cumulative epirubicin dose of > 900mg/m2

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion.

Dose Modifications:

· Epirubicin - Moderate liver impairment (bilirubin: 1.4-3 mg/100ml) give 50% of the dose, severe impairment (bilirubin> 3 mg/100 ml) give 25% of the dose.

Additional Information: Red discolouration of urine may occur for 1-2 days after administration.

Chemotherapy: CMF

*Cyclophosphamide 100mg/m2 po Days 1 to 14

Methotrexate 40mg/m2 i.v. bolus Days 1 and 8

5-fluorouracil 600mg/m2 i.v. bolus Days 1 and 8

*for patients unable to tolerate oral cyclophosphamide, substitute i.v. cyclophosphamide 600mg/m2 days 1 and 8

Repeated at 28 day intervals to a total 4 cycles if Epi-CMF and 6 cycles if CMF ALONE

Additional

Medication: Folinic acid rescue not normally required unless patients develop signs of methotrexate toxicity, then 15mg p.o. 6 hourly x 6 doses starting 24 hours post methotrexate with subsequent cycles.

Anti-emetic High emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle and FBC on day 8.

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion, but methotrexate is hazardous in the presence of renal insufficiency and presence of third space fluids.

Dose modification:

WBC ≤3.0 x 109/L and neutrophils ≤1.0 x 109/L or platelets 100 x 109/L:

- delay day 1 treatment by one week (EPI)

- cancel day 8 treatment but continue oral cyclophosphamide if possible. (CMF)

Grade 3 mucositis (EPI)

- reduce dose of epirubicin by 20%

Neutropenic sepsis (EPI)

- reduce dose of epirubicin and/or cyclophosphamide by 20%

or consider G-CSF support to maintain ≥ 85% dose intensity

Cyclophosphamide: Not recommended in patients with bilirubin >17μmol/L or serum transaminases or ALP 2-3 x ULN

GFR (ml/min) Dose

>50 100%

10-50 75%

<10 50%

Methotrexate: If bilirubin 53-84 μmol/L or AST> 180 give 75% of dose, if bilirubin >85 μmol/L omit.

Cr Cl (ml/min) Dose

>80 100%

60 65%

45 50%

<30 Contraindicated

Additional therapy and information:

Patients on sequential chemotherapy who require adjuvant radiotherapy should have this after epirubicin and during CMF (between cycles 1 & 2) or at the discretion of the clinical oncologist.

Patients may or may not have adjuvant hormonal therapy upon completion of chemotherapy.

1. Bonnadonna G et al. JAMA 1995; 273(7): 542-7

2. National Breast Cancer Study of Epirubicin + CMF vs Classical CMP Adjuvant Therapy, CRC BR3014

FEC 75

Patient group: PS 0-1

Older patients

Unsuitable for Epi-CMF

Chemotherapy:

5-fluorouracil 600mg/m2 i.v. bolus over 3-5 minutes Day 1

Epirubicin 75mg/m2 i.v. bolus over 3-5 minutes Day 1

Cyclophosphamide 600mg/m2 i.v. bolus over 3-5 minutes Day 1

Repeat at 21-day intervals for 6 cycles

Additional

Medication: Prophylactic ciprofloxacin 500mg po twice daily days 8 - 14

Anti-emetic: High emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle.

· LV ejection fraction prior to first cycle if patient has history of cardiac problems. Risk of cardiomyopathy increases with cumulative epirubicin dose of > 900mg/m2

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion.

Dose Modifications:

· Epirubicin: Moderate liver impairment (bilirubin: 1.4-3 mg/100ml) give 50% of the dose, severe impairment (bilirubin> 3 mg/100 ml) give 25% of the dose.

· Cyclophosphamide: Not recommended in patients with bilirubin >17μmol/L or serum transaminases or ALP 2-3 x ULN

GFR (ml/min) Dose

>50 100%

10-50 75%

<10 50%

Additional Information: Red discolouration of urine may occur for 1-2 days after administration

1. Early Breast Cancer Trialists Collaborative Group. Lancet 1998; 352: 930-42

2. Levine MN, Bramwell VH, Pritchard KL et al. J Clin Oncol 1998; 16: 2651-8

3 .Bonneterre J et al. Epirubicin increases long-term survival in adjuvant chemotherapy with poor-prognosis, node positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study group 05 randomised trial. JCO 2005; 23: 2686 – 2693

4. French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5 year follow-up results of French Adjuvant Study Group 05 randomized trial. JCO 2001; 19: 602 – 611

FEC/DOCETAXEL

Patient group: As per NICE guidance

· High risk

· Node positive

· PS 0 – 1

Chemotherapy: 5-fluorouracil 500mg/m2 i.v. bolus over 3-5 minutes Day 1

Epirubicin 100mg/m2 i.v. bolus over 3-5 minutes Day 1

Cyclophosphamide 500mg/m2 i.v. bolus over 3-5 minutes Day 1

Additional Information: Red discolouration of urine may occur for 1-2 days after administration

Repeat at 21-day intervals for 3 cycles

followed by

Pre-medication: Dexamethasone 8mg po twice daily for 3 days starting the day before treatment. Required for all cycles.

Chemotherapy: Docetaxel 100mg/m2 i.v. infusion over 60 minutes Day 1

Repeat for 3 cycles at 21-day intervals

Additional

Medication: Prophylactic ciprofloxacin 500mg po twice daily for 7 days starting day 5

Anti-emetic: High emetic potential

Investigations:

· Weight, FBC, U&E’s, LFT’s before each cycle.

· LV ejection fraction prior to first cycle if patient has history of cardiac problems. Risk of cardiomyopathy increases with cumulative epirubicin dose of > 900mg/m2

· Where renal/hepatic function is abnormal, treatment is at consultant physician discretion.

Dose Modifications:

· Neutrophils < 1.0 x 109/L defer dose

Platelets < 100 x 109/L defer dose

AST or ALT > 1.5 x upper limit normal reduce dose by 25%

> 3.5 x upper limit normal discontinue

· Epirubicin: Moderate liver impairment (bilirubin: 1.4-3 mg/100ml) give 50% of the dose, severe impairment (bilirubin> 3 mg/100 ml) give 25% of the dose.

· Cyclophosphamide: Not recommended in patients with bilirubin >17μmol/L or serum transaminases or ALP 2-3 x ULN

GFR (ml/min) Dose

>50 100%

10-50 75%

<10 50%

· Docetaxel: If ALT/AST > 1.5 x ULN and ALP 2.5 x ULN give 75% of dose. If bilirubin > 22μmol/L +/- ALT/AST> 3.5 x ULN with ALP > 6 x ULN contraindicated.

Non-haematological toxicities (excluding alopecia):if necessary delay treatment by one or more weeks until recovery to grade 0 or 1; if recovery takes longer than one week or if toxicity of grade 3+ is documented during chemotherapy, the dose should be reduced by 20% in all subsequent cycles.

1. Roche H et al.Breast Cancer Res Treat, 2004; abstract 270; 88 supl 1:S16

TRASTUZAMAB

Patient profile: Women with primary breast cancer who