Docetaxel + Carboplatin + Trastuzumab

Transcription

1 Docetaxel + Carboplatin + Trastuzumab Available for Routine Use in Burton in-patient Derby in-patient Burton day-case Derby day-case Burton community Derby community Burton out-patient Derby out-patient Indication HER-2 +ve Breast Cancer Treatment Intent Adjuvant Anti-Emetics Pre-chemotherapy Day 1 3 Post-chemotherapy Day 1 A Day 0 Trastuzumab 8mg/kg Intravenous infusion in 250ml sodium chloride 0.9% over 90 minutes (Cycle 1 only) Dexamethasone 8mg Oral twice daily, starting 24 hours prior to docetaxel & continued for a total of six doses (3days) Day 1 Trastuzumab 6mg/kg Intravenous infusion in 250ml sodium chloride 0.9% over 30 minutes* (Cycle 2 onwards) Docetaxel 75mg/m 2 Intravenous infusion in 250ml sodium chloride 0.9% over 60 minutes Day 3 Carboplatin Dose = AUC * (GFR + 25) mg (See notes below) GCSF 300 micrograms Intravenous infusion in 500ml Dextrose 5% over 30 minutes Subcutaneous injection ONCE daily for 7 days * If the initial dose of Trastuzumab is not well tolerated, continue to administer subsequent doses over 90 minutes (Ref. SPC Herceptin) Frequency & duration: every 21 days for a maximum of 6 cycles (chemo only)(see notes below) Herceptin to continue for 12 months Notes: 1. FBC, U&Es and LFTs must be taken prior to Day 1 of each cycle. PAGE 1 of 6

2 2. Docetaxel should be given for 6 cycles, with Trastuzumab therapy continuing for a total of 18 doses 3. For cycles 2 to 6, Trastuzumab should be administered before docetaxel 4. If the first cycle of chemotherapy is well tolerated, Trastuzumab and docetaxel may both be given on day 1 for subsequent cycles 5. Carboplatin dosage based on EDTA renogram prior to cycle 1. If the isotopic clearance is measured then the value uncorrected for body surface area (BSA) should be used in dose calculations. The Cockcroft Gault formula may be used to calculate at the Clinicians discretion. e.g. Cockcroft Gault Formula Females: Males: 1.04 x (140 age) x weight (kg) serum creatinine (micromol/l) 1.23 x (140 age) x weight (kg) serum creatinine (micromol/l) For patients with body mass index (BMI) of 30 kg/m2 with stable serum creatinine values, the adjusted body weight (ABW) should be used to estimate the GFR i.e. Ideal Body Weight Female IBW (kg) = Height in cm Male IBW (kg) = Height in cm 100 ABW = IBW + 0.4(actual weight IBW If the estimated serum creatinine clearance is <60 ml/minute, then a formal measurement of the GFR should be considered, using either a 24 hour urine collection or an isotopic clearance. If the isotopic clearance is measured then the value uncorrected for body surface area (BSA) should be used in dose calculations. 6. The GFR should be recalculated, or re-measured, for Renal toxicity (CTC Grade 2, serum creatinine >1.5 x ULN), Serum creatinine changes of 10% compared to baseline, or last creatinine value used to calculate carboplatin dose (whichever is most recent), PAGE 2 of 6

3 Each dose modification of carboplatin, Cycle 2, if there has been significant doubt about the true GFR at cycle 1 (according to clinical judgement). 7. AUC = 5 to 6 in accordance with EMCN guidelines. 8. Dose Modifications as per NCI Common Toxicity Criteria. Stomatitis & Mucositis For Grade III Painful erythema or ulcers requiring IV rehydration resolving to Grade I or less painless ulcers or mild soreness. 20% reduction Docetaxel Peripheral Neuropathy Grade 0,1 no change Grade 2-20% reduction Docetaxel Grade 3 discontinue treatment Cutaneous reactions Grade 0,1,2 no change Grade 3 delay treatment for maximum 2 weeks until at least Grade 1 & restart with 20% reduction Docetaxel. Other Toxicities For Grade III toxicity re-treat at 20% dose reduction provided toxicity has resolved to Grade I or less. If further toxicity an additional reduction may be made. If necessary a delay of the next cycle for up to 2 weeks to allow recovery. 9. If a delay of more than 3 weeks is required for recovery or more than 2 dose reductions are necessary, then the patient should discontinue docetaxel treatment. 10. Hypersensitivity reactions with Docetaxel (This is rare with premedication, but when it occurs it is usually within the first few minutes of Infusion in either Cycle 1 or 2.) MILD symptoms Decrease rate of infusion & monitor patient until Skin rash,flushing or pruritis MODERATE symptoms Generalised pruritis or rash, dyspnoea, mild hypotension SEVERE symptoms Bronchospasm, generalised urticaria, angio-oedema, hypotension (systolic < 80mmHg) recovery- then continue as before STOP docetaxel infusion & give IV antihistamine & steroids- resume docetaxel after recovery- for further cycles give IV antihistamine & steroids 1 hour prior to infusion plus usual premedication STOP docetaxel infusion & give IV antihistamine & steroids as above give adrenaline & salbutamol (if wheezing) - IV fluids may be necessary for hypotension PAGE 3 of 6

4 N.B. After a severe hypersensitivity reaction the patient must be withdrawn from the protocol treatment. 11. Contra-indications to adjuvant trastuzumab History of o Symptomatic heart failure o Myocardial infarction within last 12 months o Angina requiring regular treatment o Arrhythmia requiring regular treatment o Clinically significant valvular disease o Poorly controlled hypertension (systolic >180mmHg or diastolic >100mmHg) o Cardiomegaly on CXR o ECG evidence of LBBB or large territory infarct 12. All cases considered fit to receive Trastuzumab should have immunohistochemistry (IHC) performed on biopsy samples to confirm HER-2 status. Those who have a positive result would be eligible for Trastuzumab. Those with a borderline result (approx. 20% of cases) require Fluorescence in situ hybridisation (FISH) testing in addition to determine the HER2 status of the sample 13. Provided the initial dose of trastuzumab is tolerated, subsequent doses may be administered over 30 minutes. 14. The use of Trastuzumab is associated with cardiotoxicity. All candidates for treatment should undergo careful cardiac monitoring. Cardiac monitoring with echocardiography or MUGA scanning in accordance with local protocol should be carried out at baseline and then at three monthly intervals during therapy (i.e. 3, 6, 9 and 12 months). Patients will go ahead with adjuvant trastuzumab providing that the baseline LVEF (on MUGA scan or ECHO) is at least 55% A guideline for stopping treatment in the event of reduced cardiac function based on the HERA trial protocol is as follows: PAGE 4 of 6

5 Asymptomatic patients LVEF Absolute decrease from baseline result of <10% Absolute decrease from baseline result of 10-15% Absolute decrease from baseline result of 16% Within normal limits Continue Continue Hold* 1-5% below normal limits 6% below normal limits Continue Hold* Hold* Continue* Hold* Hold* *repeat LVEF assessment before 6 weeks. e.g. Baseline LVEF 70%, Subsequent LVEF 63% = Absolute decrease of 7% If criteria for continuation are met resume trastuzumab. If 2 consecutive holds or a total of 3 holds occur, discontinue trastuzumab. Symptomatic patients Patients who develop symptomatic cardiac dysfunction should have trastuzumab discontinued and be referred to a cardiologist. 15. Patients should be observed for at least six hours after the start of the first infusion and for two hours after the start of the subsequent infusions for symptoms like fever and chills or other infusion-related symptoms 16. Infusion related reactions During the first infusion of Trastuzumab chills and/or fever are observed commonly in patients. Other signs and symptoms may include nausea, hypertension, vomiting, pain, rigors, headache, cough, dizziness, rash, and asthenia. These symptoms are usually mild to moderate in severity, and occur infrequently with subsequent Trastuzumab infusions. These symptoms can be treated with an analgesic/antipyretic such as pethidine (50mg intravenous bolus) or paracetamol (1g oral stat dose), or an antihistamine such as chlorphenamine (10mg intravenous bolus) Some adverse reactions to Trastuzumab infusion including dyspnoea, hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation and respiratory distress can be serious and potentially fatal, contact a doctor if these symptoms are observed. PAGE 5 of 6

6 References: 1. L. Y. Dirix et al. ; Phase II study of docetaxel, carboplatin and trastuzumab (THC) in patients with locally advanced breast cancer.; Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1062 PAGE 6 of 6