West of Scotland Cancer Network Chemotherapy Protocol

Transcription

1 West of Scotland Cancer Network Chemotherapy Protocol DOCETAXEL/TRASTUZUMAB (BRWOS-005/1) Indication Docetaxel in combination with is indicated for the treatment of patients with HER2 overexpressing locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Eligibility Criteria Previous treatment should have included an adjuvant or metastatic anthracycline Patients who are HER2-ve,HER2 1+ OR HER2+ without amplification Patients with HER2 3+ or have gene amplification on FISH testing MUGA/LVEF >55% Exclusion Criteria Performance status > 2 Hypersensitivity to other taxane based therapies HER2 ve patients Patients with the following: Documented cardiac failure High risk uncontrolled arrhythmias Angina pectoris requiring medication Clinically significant valvular disease Evidence of transmural myocardial infarction on ECG Uncontrolled hypertension Dyspnoea at rest increases risk of fatal infusion related reactions to Pre-treatment evaluation Multi disciplinary review and histological information Give adequate verbal and written information for patients and their relatives regarding the patients disease, treatment and side effects Obtain written consent Formal evaluation of disease, clinical examination Document WHO performance status,height, weight and BSA If appropriate discuss potential risk of infertility/early menopause with patients Baseline investigations should include- FBC( neutrophils > 1.5, can be given if neutrophils between but only at prescribers discretion, platelets > 100), U&E s, LFT s,serum creatinine, Creatinine Clearance (>30mls/min) 1

2 Regimen Pre medication of Dexamethasone 8mg BD should be given for 3 days starting the night before Docetaxel therapy Drug Dose Route Administration Day to be given Maximum cumulative dose Docetaxel 100mg/m 2 IV IV infusion in NaCl 0.9% 250ml over 1 hour 8mg/kg (loading dose) IV IV infusion 250ml NaCL 0.9% OVER 90 MINS Day 1 Loading dose week 1 6mg/kg (every 21 days) IV IV infusion 250ml over 90mins Subsequent Weeks Day 1 As both drugs may cause hypersensitivity reactions consider giving the first dose of each drug on separate days. If there is no reaction subsequent doses may be given on the same day Repeat every 21 days for 6 cycles Stop if disease progression or unable to tolerate treatment The patient 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. If the patient misses a dose of by one week or less, then the usual dose of (6 mg/kg) should be given as soon as possible (do not wait until the next planned cycle). Subsequent maintenance doses of 6 mg/kg should then be given every 3 weeks, according to the previous schedule. If the patient misses a dose of by more than one week, a re-loading dose of should be given (8 mg/kg over approximately 90 minutes). Subsequent maintenance doses of 6 mg/kg should then be given 3 weeks from that point. Emetogenic risk moderate refer to local policy Can offer scalp cooling Give anti emetics according to local protocol Give supportive therapy according to local protocols Is GCSF indicated? Primary prophylaxis Not recommended. Consider dose reduction instead. Secondary prophylaxis Not recommended. Consider dose reduction instead. Stem cell mobilisation Other supportive treatment: None Adverse effects Common Uncommon Lethargy, myelosuppression, total alopecia, mucositis, mild-moderate emesis, myalgia, fluid retention, altered bowel pattern, skin and nail changes, myalgia, increased sensitivity to strong sunlight, taste disturbance,altered menstrual cycle,fertility changes, hypersensitivity (see local protocol for management),hand/foot syndrome peripheral neuropathy,tear production,headache 2

3 For more detailed information refer to the full current Summary of Product Characteristics Extravasation risk category Drug Docetaxel Category Exfoliant Non-vesicant In event of an extravasation, refer to local extravastion policy Precautions & contraindications Hypersensitivity reactions are common. Patients should be observed closely especially during the first and second infusion. These reactions may occur within a few minutes of the initiation of the infusion, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reactions occur with Docetaxel, minor symptoms such as flushing or localised cutaneous reactions do not require interruption of therapy. However, severe reactions such as severe hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of docetaxel and appropriate therapy. Patients who develop severe hypersensitivity reactions should not be re-challenged with Docetaxel. If the patient develops an infusion related reaction (eg fever, chills) with 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 If bilirubin > ULN then use Docetaxel with extreme caution Pregnancy and lactation contraceptive measures should be taken Investigations prior to subsequent cycles FBC, LFT S, U & E s performance status assessment of toxicity, documented by CTC criteria version 3.,0 Drug Interactions Docetaxel - There is potential for interaction with drugs that are metabolised by cytochrome p450 eg) ketoconazole,erythromycin and therefore these drugs should be avoided or stopped -Drug interaction are unknown See BNF for full details or check with pharmacy 3

4 Dose modifications Haematology Result Value Action Platelets x 10 9 /L < 100 Delay treatment until platelets recover Neutrophils < 1 Delay treatment until neutrophils recover. Subsequent occurrence consider 20% dose reduction of Docetaxel only. Grade 4 neutropenia with sepsis Neutrophils < 1.0 and fever 38.5 C Delay until recovered then retreat at 80% Docetaxel dose/full dose Herceptin Renal Function Drug GFR % of full dose Comments No dose reduction required in renal impairment Docetaxel No dose reduction necessary Hepatic Function AST and/or ALT values Alkaline phosphatase values Docetaxel Dose modification 1.5 x ULN AND 5 x ULN no dose modification >1.5 x ULN x ULN AND 2.5 x ULN no dose modification >2.5 x ULN - 5 x ULN AND 2.5 x ULN reduce by 25% (not below 55 mg/m 2 ) >1.5 x ULN - 5 x ULN AND >2.5 x ULN - 5 x ULN reduce by 25% (not below 55 mg/m 2 ) >5 x ULN OR >5 x ULN (unless bone metastasis are present in the absence of any liver disorder) delay dose by a maximum of 2 weeks. If no recovery, discontinue docetaxel. -use with caution Toxicities Toxicity Grade Action Nausea and vomiting 1 or above Increase/change antiemetics. No dose reduction. Any Grade 3 resolving to grade 1 Consider 20% dose reduction depending on toxicity 4

5 Any Grade 4 Refer to consultant Infusion related reaction Stop infusion until symptoms improve, restart at Same or lower rate Neuropathy Grade 2 Consider 20% dose reduction Evaluation of response to treatment to be reviewed by oncologist each cycle formally re-evaluate after 3-6 cycles References Extra JM, Cognetti F, Chan S, et al. First-line trastuzumab (Herceptin) plus docetaxel versus docetaxel alone in women with HER2-positive metastatic breast cancer (MBC): results from a randomised phase II trial (M77001). Breast Cancer Res Treat. 2003;82(suppl 1):S47. Abstract 217 Extra JM, Cognetti F, Maraninchi D et al. Long-term survival demonstrated with trastuzumab plus docetaxel: 24-month data from a randomised trial (M77001) in HER2-positive metastatic breast cancer. Abstract #555, American Society for Clinical Oncology (ASCO) Annual Meeting 2005 ABPI Medicines Compendium 2005 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 Written by Gillian Barmack, Judy Fraser,Joanne Low Approved by Mohammed Rizwanullah on behalf of the BOC breast team Date : March 2007 Review date: March