West of Scotland Cancer Network Systemic Anti-Cancer Therapy Protocol

Transcription

1 West of Scotland Cancer Network Systemic Anti-Cancer Therapy Protocol FEC-DH in the adjuvant treatment of Breast Cancer (BRWOS- 031/1) Indication Adjuvant chemotherapy for HER2+ve Early Breast Cancer Eligibility Inclusion criteria Patients post mastectomy or wide local excision with HER2 3+ or HER2 2+ with gene amplification on FISH testing and node positive disease Performance status 0-1 Age <65 years Good cardiac function, as defined by cardiac ejection fraction of >55% (refer to Appendix 1 Trastuzumab cardiac guideline for further information) Exclusion criteria HER2 ve, HER2 1+ or HER2 2+ without gene amplification Node negative tumours Patients with an ejection fraction of <55% should not receive anthracyclines Performance status >1 Age 65 years Treatment Intent Adjuvant Pre-treatment evaluation Informed consent, provision of verbal and written information Assessment of performance status Height, weight and BSA Baseline investigations FBC (neutrophils > 1.0, platelets > 100), U&E s, LFT s,serum creatinine) Assessment of cardiac ejection fraction by MUGA or ECHO If appropriate discuss potential risk of infertility/early menopause with patients Page 1 of 7

2 Regimen Cycle Drug Dose Route Administrat ion 1-3 Fluorouracil 500mg/m 2 IV Bolus via fast r unning drip 1-3 Epirubicin 100mg/m 2 IV Bolus via fast r unning drip 1-3 Cyclophosphamide 500mg/m 2 IV Bolus via fast running drip Repeat every 21 days for 3 cycles then Day to be given Day 1 only Day 1 only Day 1 only Maximum cumulative dose 900mg/m 2 Cycle Drug Dose Route Administration Day to be given 4 Trastuzumab 8mg/kg IV Over 90 minutes in Day 1 250ml Sodium Chloride 0.9% 5-6 Trastuzumab 6mg/kg IV Over 60 mins Day 1 initially then 30 mins for subsequent cycles, if tolerated, in 250ml Sodium Chloride 0.9% 4-6 Docetaxel 100mg/ IV Over 60 minutes in Day 1 m 2 250ml Sodium Chloride 0.9% Maximum cumulative dose Repeat every 21 days f or cycles 4-6 Cycle Drug Dose Route Administration Day to be given Page 2 of 7 Maximum cumulative dose 7-21 Trastuzumab 6mg/kg IV Over 30 minutes in Day 1 250ml Sodium Chloride 0.9% Repeat every 21 days for a total of 18 doses Trastuzumab. Trastuzumab may be started either at cycle 4 (ie. cycle 1 docetaxel) or at cycle 5 (ie. cycle 2 docetaxel). The duration of the first infusion is 90 minutes, and a minimum of 60 minutes is recommended be allowed to pass following completion of the infusion before starting docetaxel infusion. Patients should be monitored for reactions such as fever or chills or other infusion related reactions for 6 hours after the start of the initial infusion and for 2 hours after the start of subsequent infusions. The second infusion may be administered intravenously over 60 minutes, and the

3 docetaxel infusion is recommended to be started 30 minutes after completion of infusion. The third docetaxel infusion may be started immediately after completion of the infusion provided that no toxicity is detectable. The duration of the third and subsequent infusions is 30 mins provided that the first two infusions have been tolerated. Pre medication of Dexamethasone 8mg twice daily should be given for 3 days starting the night before Docetaxel therapy to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For patients experiencing Grade 3 arthralgia/myalgia patients should get a reducing dose of steroids after medical review. Day 1 Dexamethasone 8mg BD Day 2 Dexamethasone 8mg BD Day 3 Dexamethasone 6mg 4mg Day 4 Dexamethasone 4mg 4mg Day 5 Dexamethasone 2mg 2mg If the patient misses a dose of Trastuzumab by one week or less, then the usual dose of Trastuzumab (6 mg/kg) should be given as soon as possible (do not wait until the next planned cycle). Subsequent maintenance Trastuzumab doses of 6 mg/kg should then be given every 3 weeks, according to the previous schedule. If the patient misses a dose of Trastuzumab by more than one week, a re-loading dose of Trastuzumab should be given (8 mg/kg over approximately 90 minutes). Subsequent maintenance Trastuzumab doses of 6 mg/kg should then be given 3 weeks from that point. Emetogenic Risk: FEC Moderate, Docetaxel + Trastuzumab - minimal refer to local antiemetic policy Is GCSF indicated? Primary prophylaxis To reduce frequency of neutropenic events, primary prophylaxis is recommended for all patients from cycles 1-6. For patients receiving FEC, GCSF should be started on day 5 for 7 days. For patients receiving Docetaxel, GCSF should be started on day 3 for 7 days. Alternatively pegylated GCSF may be used as a single dose 24 hours after chemotherapy. See GCSF policy for dosing information Secondary prophylaxis. Not applicable. GCSF is not indicated when patient is on single agent Trastuzumab Adverse effects Common: Bone marrow suppression neutropenia, thrombocytopenia, anaemia, nausea and vomiting, lethargy, alopecia, mucositis, taste changes, skin and nail changes, bladder irritation, diarrhoea, gritty eyes/blurred vision, alteration to menstrual cycle and fertility, red discolouration to urine and tears, arthralgia, myalgia, infusion related reactions Uncommon: cardiotoxicity Trastuzumab: Common: abdominal pain, asthenia, chest pain, chills, fever, headache, pain, diarrhoea, nausea, vomiting, arthralgia, myalgia, rash, Uncommon: Hypersensitivity reactions, cardiotoxicity Page 3 of 7

4 If the patient develops an infusion related reaction (eg fever, chills) with Trastuzumab the infusion should be stopped until symptoms have resolved and may be restarted at the same or lower rate. Serious infusion related reactions should be treated with supportive therapy such as oxygen, beta agonists and corticosteroids Adverse effects commonly attributed to GCSF are: musculoskeletal pain and mild to moderate dysuria. For more detailed information on adverse effects refer to the full current Summary of Product Characteristics Extravasation risk category Drug Fluorouracil Epirubicin Cyclophosphamide Trastuzumab Docetaxel Category Inflammitant Vesicant Neutral Neutral Exfoliant In event of an extravasation, refer to local extravasation policy. Precautions Caution in patients with significant cardiac disease Use with extreme caution in pregnancy, avoid breastfeeding Contraceptive measures should be taken Known medicine interactions (FEC/Docetaxel/both): metronidazole (FEC), warfarin (FEC), phenytoin (both), clozapine (FEC), cimetidine (FEC), erythromycin (Docetaxel), ketoconazole (Docetaxel), ciclosporin (Docetaxel) see BNF for details Interactions with Trastuzumab are not known, use with caution Investigations prior to subsequent cycles FBC, U&E, LFT s, creatinine (cycles 1-6 then 4 monthly during Trastuzumab) performance status (every cycle) assessment of toxicity, documented by CTC criteria (every cycle) ECHO/MUGA scan to assess cardiac ejection fraction after cycle 3, prior to starting Trastuzumab. If ejection fraction less than 55% refer to Trastuzumab Cardiac Guidelines 2010 ECHO/MUGA scan should be repeated at 4 months and 8 months into treatment with Trastuzumab and where clinically indicated Refer to Trastuzumab cardiac guidelines 2010 for detailed guidance on management of cardiac dysfunction. Page 4 of 7

5 Dose modifications Hae matology Result Value Action Platelets x 10 9 /L < 100 Delay treatment until platelets recover Neutrophils x 10 9 < 1.0 Delay treatment until neutrophils recover Dose reduce subsequent cycles by 20% Neutropenic sepsis since previous cycle Neut rophils < 1.0 and fever 38.5 C Ensure reviewed by medical staff prior to authorising treatment Dose reduce subsequent cycles by 20% Renal Function Drug GFR % of full dose Comments 5 Fluorouracil <1 0 Consider dose reduction. Epirubicin <10 Consider dose reduction. Cyclophosphamid e > % 75% Consider using Mesna if GFR <20ml/min. <10 50% Trastuzumab No dose reduction necessary. Docetaxel No dose reduction necessary. Hepatic Function Drug Bilirubin (microm AST/ALT (u/l) Alk Phos % of full dose 5 Fluorouracil Moderate hepatic impairment Severe hepatic impairment 66% 50% *consider increasing dose if no toxicity Epirubicin < >85 100% 50% 25% omit Cyclophosphamide In absence of jaundice, no dose redu ction necessary Trastuzumab Use with caution no information available Docetaxel > 1.5x ULN > 2.5x ULN 75% > 22 > 3.5x ULN > 6x ULN Do not use unless strictly indicated. Other toxicities Toxicity Grade Action Nausea and vomiting 1 or above Increase/change antiemetics. No dose reduction. Any other toxicity: Consider 20% dose reduction depending on toxicity. Grade 3 resolving to grade 1 Any grade 4 Refer to consultant. Infusion related reaction Stop infusion until symptoms improve, restart at same or lower rate Page 5 of 7

6 Evaluation of response to treatment no assessment of tumour response required References Roche H, Fumoleau p, Speilmann M et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients:the FNCLCC PACS 01 Trial. J Clin Oncol 2006; 24 (36): Piccart-Gebhart M J et al. Trastuzumab after Adjuvant Chemotherapy in HER2 positive breast cancer. NEJM. 2005; 353(16): Martin et al. Toxicity and health related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol. 2006; 17(8): Summary of product characterist ics see Summerhays M, Daniels S. Practical Chemotherapy a multidisciplinary guide. Radcliffe Medical Press, Oxford Allwood M, Stanley A, Wright P (Eds) The Cytotoxic Handbook. 4th edition. Radcliffe Medical Press, Oxford Document control Prepared by Checked by Approved by Issue date November 2010 Review date November 2012 Reference/version no. BRWOS 031/1 Replaces Not Applicable Joanne Robinson Paula Morrison & Dr Sophie Barrett RCAG Prescribing Advisory Subgroup Page 6 of 7

7 EF * Trastuzumab Cardiac Guidelines PRE CHEMO POST CHEMO / DURING TRASTUZUMAB > 55% < 55% but > 40% (asymptomatic) Standard Chemo Consider Chemo Start ACEi Refer to Cardiology EF pre 4/12 & 8/12 <40 % No Yes < 55% but > 40 %? No > 55%? Y es Stable c/w pre-chemo &/or immed prev EF? No Yes Yes APPENDIX 1 c/w or start ACEi, Refer to Cardiology if not already. No c/w ACEi, start/restart or c/w Start/restart or c/w No < 40% Consider non-anthra chemo /no chemo Refer to Cardiology < 40% < 55% but > 55% > 40 %? > 10% drop compared with prechemo or immed prev EF LLN = 55% EF = Ejection fraction c/w = Continue with Commence ACEi, stop & refer to Cardiology Commence ACEi, Stop trastuzumub Refer to Cardiology, rpt EF after 6-8 weeks, restart only if EF returns to >55% Yes Commence ACEi, Refer to Cardiology, c/w trastuzumub, rpt EF after 6 8 weeks *Reference: Jones et al (2009) Management of cardiac health in treated patients with breast cancer: updated United Kingdom National Cancer research Institute recommendations for monitoring Br J Cancer 100: Page 7 of 7