Breast Cancer



North Wales Cancer Network

Chemotherapy Protocols

2006/07

North Wales Cancer Network

Chemotherapy Protocols -2006/7

INTRODUCTION 4

Breast Cancer Regimens 6

GASTROINTESTINAL CANCER 23

OESOPHAGEAL CANCER CHEMOTHERAPY REGIMENS 23

PANCREATIC CANCER CHEMOTHERAPY REGIMENS 31

1. Burris HA, et al. J Clin oncol 1997; 15(6): 2403-13 33

2. National Institute for Health and Clinical Excellence, Guidance on gemcitabine for pancreatic cancer. 2001 33

Colorectal cancer chemotherapy regimens 35

GYNAECALOGICAL CANCER 42

Ovarian Cancer Chemotherapy Regimens 42

Endometrial Cancer Chemotherapy Regimens 46

Cervical Cancer Chemotherapy Regimens 48

Small Cell Lung Cancer Chemotherapy regimens 50

Non-small Cell Lung Cancer Treatment regimens 51

Mesothelioma Chemotherapy Regimens 53

Head and Neck Cancer Chemotherapy Regimes 54

BLADDER CANCER CHEMOTHERAPY Regimens 56

renal cancer Chemotherapy Regimens 59

Prostate Cancer Chemotherapy Regimens 59

Germ Cell Tumour Chemotherapy Regimens 61

mALIGNANT MELANOMA CHEMOTHERAPY REGIMENS 63

BILLIARY TREE CHEMOTHERAPY REGIMES 67

COCKCROFT-GAULT CREATININE CLEARANCE FORMULA 68

CISPLATIN DOSE GUIDELINES 69

HAEMATOLOGICAL PARAMETERS 70

ANTI-EMETIC POLICY FOR CYTOTOXIC CHEMOTHERAPY 71

INTRATHECAL CHEMOTHERAPY 72

PLATELET TRANSFUSION POLICY 73

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.

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 or prescriptive document and should not utilised in anyway as a formal guide to prescribing.

This list contains the protocols which are available and funded for use during the year beginning April 1st 2006 to March 31st 2007. With the exception of drug/regime assessments from NICE, there will be generally no alterations during the current year.

All oncologists will be canvassed during November, for any changes, additions or deletions for the protocol list commencing April 2007.

Exclusions

The formulary largely concentrates on regimen used as first and second line. The formulary recognises that third line or indvidualised use of chemotherapy is more difficult to standardise and this therefore is omitted.

This approach also extends to certain other elements of oncology, haemato-oncology and supportive care though these issues will be addressed in future versions.

Future inclusions

It is hoped that future versions will include sections on,

• Haemato-oncology chemotherapy

• Use of blood products

• Pain control

• Use of growth factors

Resource issues.

All the regimens within this formulary are funded and this includes all NICE drugs approved up to the point of publication July 2006.

However though all the protocols are funded and therefore available it cannot be automatically assumed that all the protocols 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 patient sin North Wales in 2006/07. In doing so these regimens should be available in all three Trusts assuming clinical governance and capacity parameters are met.

New drugs

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

Breast Cancer Regimens

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

EC

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 three cycles, consider switching to docetaxel

Chemotherapy Epirubicin 75mg/m2

Cyclophosphamide 600mg/m2

repeated at 21 day intervals x 4-6 cycles

Anti-emetics for high emetic potental

Investigations

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

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

DOCETAXEL

Chemotherapy: Docetaxel 100mg/m2 for 4 cycles

Dexamethasone 8mg bd x 3 days. Start 24 hours pre docetaxel

Prophylactic ciprofloxacin 500mg po twice daily days 5 - 14

Anti-emetic for intermediate emetic potental

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 during chemotherapy, the dose should be reduced by 20% in all subsequent cycles.

Adjuvant

EPI-CMF

Patient group: First choice

Node –ve tumours

Chemotherapy: Epirubicin 100mg/m2 repeated at 21 day intervals x 4 cycles

Followed by CMF 4 cycles (Classical Bonnadonna)

Anti-emetic for high emetic potental

Investigations

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

• Where renal/hepatic function are abnormal, treatment is at the consultant physician discretion.

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

Chemotherapy: CMF

Cyclophosphamide 100mg/m2 po days 1 to 14

Methotrexate 40mg/m2 iv days 1 and 8

5 fluorouracil 600mg/m2 iv days 1 and 8

cycles are repeated at 28 day intervals from day 1 to a total of 6 cycles

for patients unable to tolerate oral cyclophosphamide, substitute iv cyclophosphamide 600mg/m2 days 1 and 8

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

Anti-emetic for high emetic potental

Investigations

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

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

• prior to each cycle but generally not required on day 8

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

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 tamoxifen. This would normally be started on 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

Patient group: PS 0-1

Older patients

Unsuitable for Epi-CMF

Chemotherapy: 5 fluorouracil 600mg/m2

epirubicin 60mg/m2

cyclophosphamide 600mg/m2

repeat at 21 day intervals for 6 cycles

anti-emetic: for high emetic potential

Investigations

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

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

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

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

NB: see above for dose modifications and precautions.

FEC/DOCETAXEL

Patient group: This protocol is available for young women wishing to maintain fertility or where previous treatment restricts anthracycline dose.

• Node positive

• ER –ve

• PS 0 – 1

Selected patients only (restricted, not NICE)

Chemotherapy: 5 fluorouracil 500mg/m2

epirubicin 100mg/m2

cyclophosphamide 500mg/m2

repeat at 21 day intervals for 3 cycles

followed by

docetaxel 100mg/m2 x 3 cycles at 21 day intervals

Dexamethasone 8mg bd x 3 days. Start 24 hours pre-docetaxel.

Prophylactic ciprofloxacin 500mg po twice daily days 5 - 14

Anti-emetic: for high emetic potential

NB: see above for laboratory investigations

See above for dose modifications and precautions.

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

TRASTUZAMAB

Patient profile: Women with primary breast cancer

• Over expressing HER-2 (3+ on IHC or FISH +)

• Completed (neo)adjuvant chemotherapy within the preceding 6 weeks

• LVEF measured by echocardiography or MUGA ≥ 55%

• ER+ women to be receiving appropriate hormonal therapy

• Willing to undergo cardiac monitoring and regular follow up

• No history of allergy to mice or mouse proteins

Chemotherapy: Trastuzumab Initial dose: 8mg/kg over 90 minutes

Subsequent: 6mg/kg q 21 days for 18 doses

Reload if dose delayed by > 7 days.

Antiemetic Low emetic potential

1. National Institute for Health and Clinical Excellence.bTrastuzumab for the adjuvant treatment of early stage HER2-positive Breast Cancer. TA107; August 2006

Hormonal treatments

Please refer to The Use of Hormone Therapy for Breast Cancer

METASTATIC/ADVANCED DISEASE

EC

Patient group: Standard chemotherapy

Anthracycline naive

Chemotherapy: epirubicin 75mg/m2

Cyclophosphamide 600mg/m2

Repeat at 21 day intervals to a maximum of 6 cycles

Anti-emetics For intermediate emesis protection

Investigations

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

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

1. Fisher B et al. J Clin Oncol 1990; 8: 2483-96

2. UKCCCR ABO1 Breast Cancer trial (1996)

EPIRUBICIN

Patient group: For patients with compromised liver or marrow function due to tumour infiltration.

Combination therapy inappropriate

Chemotherapy: Epirubicin 20 - 25mg/m2 weekly

Anti-emetics For intermediate emesis protection

Investigations

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

• Patients with abnormal hepatic function may be treated cautiously

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

• Normal limits for administration apply with the exception of patients with marrow infiltration. Treatment may be continued at lower platelet and neutrophil counts at treating physicians discretion.

1. Twelves CJ. Et al. British Journal of Cancer, 1989; 60(6): 938-41

2. Gasparini G. et al. Am J Clin Oncol 1991; 14(1): 38-44

3. Twelves CJ. Et al. Annals of Oncology 1991 2(9): 663-6

4. Jeonsuu H et al. J Clin Oncol, 1008; 16(12): 3720-30

MMM

Patient Group: 3rd – 4th line or unfit for other treatment

Chemotherapy: Mitomycin 7mg/m2

Methotrexate 35mg/m2

Mitomycin 7mg/m2

21 day cycle

Antiemetics: For moderate emetic control

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

1. Powles TJ et al. Royal Society of Medicine Services, 1987; International Congress and Symposium Series no. 110

2. Smith IE, Powles TJ, Oncology, 1993 Apr; 50CY: Switzerland: 9-15

DOCETAXEL/CAPECITABINE

Patient group: younger patient, NICE regimen

PS 0-1

Chemotherapy: Docetaxel 75mg/m2 iv day 1

Capecitabine 1250mg/m2 twice daily orally for 14 days. (rounded to nearest 150mg)

prophylaxis: dexamethasone 8mg po twice daily for 3 days starting the day before treatment. Required for all cycles.

Anti-emesis: for intermediate emetic potental

Repeat at 21 day cycles. Max 6 cycles.

Investigations: Weight, U&E’s, FBC, creatinine clearance, LFT’s before each cycle

Dose reductions/modifications for grade 2 toxicity or higher:

• No recovery from toxicity within 2 weeks, discontinue docetaxel

• Capecitabine doses missed should not be replaced

• Toxicity > grade 2 still present at end of 3 week cycle should have a further delay of 1 week

• Doses that have been reduced in a previous cycle should not be increased subsequently

• First event grade 2: delay until recovery (maximum 2 weeks)

• Second event grade 2: delay until recovery and restart at 75% capecitabine dose and docetaxel at 55mg/m2

• First event grade 3: delay until recovery and restart at 75% capecitabine dose and docetaxel 55mg/m2

• Third event grade 2, second event grade 3, or any 4 event: discontinue docetaxel and restart capecitabine at 50% of starting dose.

• Further events, any grade: discontinue both drugs.

1. Mational Institute for Health and Clinical Excellence. Technology Apraisal no. 62 May 2003

2. O’Shaughnessy L et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline pretreated patients with advanced breast cancer. J.Clin. Oncol. 2002;20(12):2812-2823

PACLITAXEL/GEMCITABINE

Less myelosuppressive than docetaxel/capecitabine

Patient group:

• Usually given after an anthracycline containing regime

• PS = 0, 1, 2

• May also be given third line after a vinorelbine containing regime.

Chemotherapy: Paclitaxel 90mg/m2 days 1 and 8

Gemcitabine 1000mg/m2 days 1 and 8

Pre-medication to be given 30 minutes before paclitaxel:

Dexamethasone 16mg iv

Ranitidine 50mg iv

Chlorpheniramine 10mg iv

Repeat at 21 day intervals

Anti-emetic: for intermediate emetic control

Laboratory investigations

• Fbc, U&E,LFT prior to each cycle

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

Dose Modifications:

• Day 1: if WBC ................
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