CAPECITABINE (METASTATIC BREAST CANCER) (BRWOS-002/1)

Transcription

1 West of Scotland Cancer Network Chemotherapy Protocol Indication CAPECITABINE (METASTATIC BREAST CANCER) (BRWOS-002/1) Capecitabine (Xeloda) monotherapy is indicated for the treatment of locally advanced or metastatic breast cancer in patients who have failed or are not candidate for standard anthracycline containing therapy. Eligibility Criteria In patients who have failed or are not candidate for standard anthracycline containing therapy. Performance status 0-3 Exclusion Criteria Pregnant or lactating females / women of child bearing potential not using a contraceptive method Clinically significant cardiac disease uncontrolled coronary heart disease, unstable angina or myocardial infarction within last 6 months Malabsorption syndrome or inability to comply with oral medication Known or suspected DPD deficiency Other intercurrent serious illness which in the opinion of the treating consultant would render patient at risk of severe toxicity History of significant psychiatric disorders Performance status >3 Patients with severe renal impairment (creatinine clearance below 30 ml/min Cockcroft and Gault), Hypersensitivity to Capecitabine or 5-Fluorouracil Treatment with SORIVUDINE or its chemically related analogues, such as brivudine. History of severe and unexpected reactions to fluoropyrimidine therapy, In patients with severe leucopenia, neutropenia or thrombocytopenia 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, platelets > 100), U&E s, LFT s,serum creatinine, Creatinine Clearance (>30mls/min) 1

2 Regimen Drug Dose Route Administration Day to be Maximum cumulative given dose CAPECITABINE 1250mg/m 2 Oral BD 1-14 N/A Capecitabine can also be prescribed at 1000mg/m 2.This dose is not licensed however clinical experience is shown that patients tolerate this regime better whilst retaining efficacy and response. Repeat every 21 days for 4 8 cycles (treatment can continue if patient is responding to treatment and has little toxicity). Stop if disease progression or unable to tolerate Take with plenty of water within 30 minutes of eating Tablet sizes available are 150mg and 500mg Dose Banding Nomogram calculate BSA (cap at 2 m 2 ) and select dose from table below B.S.A. (m 2 ) Starting Dose per administration 1250mg/m mg/m 2 </= >/= mg 1650mg 1800mg 2000mg 2300mg 2500mg 2650mg 2800mg 1300mg 1300mg 1450mg/1500mg 1500mg/1650mg 1650mg/1800mg 1800mg/2000mg 2000mg Emetogenic risk low Give anti emetics according to local protocol Is GCSF indicated? Primary prophylaxis Not recommended. Consider dose reduction instead. Secondary prophylaxis Not recommended. Consider dose reduction instead. Stem cell mobilisation N/A Other supportive treatment: None Adverse effects Common Uncommon Lethargy, mucositis/stomatitis, nausea and vomiting, altered bowel pattern diarrhoea, abdominal pain, hand/foot syndrome, skin and nail changes, Increased sensitivity to strong sunlight, taste disturbance, fertility changes altered menstrual cycle, myelosuppression, hair thinning headaches, tear production 2

3 Palmar-plantar erythrodysaesthesia should initially be managed by appropriate dose reduction see dose modifications. Pyridoxine 50 mg three times daily may have additional benefit for symptomatic relief For more detailed information refer to the full current Summary of Product Characteristics Extravasation risk category Drug CAPECITABINE Category N/A Precautions Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiac shock, sudden death and ECG changes caution should be exercised in those patients with significant cardiac disease. There is a lack of safety and efficacy data in patients with hepatic impairment therefore use of Capecitabine should be carefully monitored. Drug Interactions Drug Interaction Action SOROVUDINE AND ANALOGUES INHIBITION OF DIHYDROPYRIMIDINE DEHYDROGENASE AVOID CONCOMITANT USE POTENTIALLY FATAL Phenytoin Folinic Acid Coumarin-derivative anticoagulants Antacids Allopurinol See BNF for full details or check with pharmacy Increase in plasma phenytoin concentration Potential for increased capecitabine toxicity Increase in INR can occur up to one month after stopping capecitabine therapy Increase capecitabine concentration Decreased efficacy of Capecitabine - theoretical Regular monitoring of plasma phenytoin levels Avoid concomitant use where possible Monitor INR twice weekly Not to be taken at same time of day Review risk of recurrence of Gout avoid concomitant use where possible. Investigations prior to subsequent cycles FBC, U&E, LFT, CrCl performance status assessment of toxicity, documented by CTC criteria version 3.0 3

4 Dose modifications Haematology Result Value Action Platelets x 10 9 /L < 100 Delay treatment until platelets recover Neutrophils < 1.5 Delay treatment until neutrophils recover. Subsequent occurrence consider 20% dose reduction. Neutropenic sepsis since previous cycle Renal Function Neutrophils < 1.0 and fever 38.5 C Refer to Consultant Drug GFR % of full dose Comments Capecitabine >50 100% % <30 Contra indicated Hepatic function Transient increases in bilirubin and/or AST/ALT are common with Capecitabine Drug Bilirubin AST/ALT % of full dose Comments Capecitabine > 3 ULN > 2.5 ULN discontinue Treatment may be restarted at full dose when bilirubin < 3 ULN or AST/ALT < 2.5 ULN Nom Haematological Toxicities Common Toxicity Criteria (CTCAE Version 3) During a course of treatment Dose adjustments (%age of starting dose) GRADE 1 Maintain dose level 100% GRADE 2 1 st appearance 100% 4 th 2 nd 3 rd GRADE 3 1 st appearance 2 nd 3 rd GRADE 4 1 ST appearance Discontinue permanently Discontinue permanently Discontinue permanently or Interrupt until 0 or 1 at clinicians discretion 75% 75% 4

5 Toxicity due to Capecitabine administration may be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced, it should not be increased at a later time. Patients taking Capecitabine should be informed of the need to interrupt treatment immediately if moderate or worse toxicity occurs. Doses of Capecitabine omitted for toxicity are not replaced or restored, instead the patient should resume the planned treatment cycle. Evaluation of response to treatment Review by oncologist every cycle Formally re-evaluate every 4 cycles CT scan References ABPI MEDICINES COMPENDIUM 2005 Blum JL, Jones SE, Budzar AV et al Multicentre phase 2 study of Capecitabine in Paclitaxel,refractory metastatic breast cancer J Clin Oncol ; 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