Capecitabine + Concurrent Radiotherapy

Transcription

1 Capecitabine + Concurrent Radiotherapy 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 Colorectal cancer Or Pancreatic Treatment Intent Adjuvant Locally advanced (Following induction chemotherapy) Anti-Emetics Pre-chemotherapy Nil Post-chemotherapy A Day 1-5 (Mon-Fri) Capecitabine 900mg/m 2 Oral every 12 hours (10 doses per week) Frequency & duration: radiotherapy) Every Mon-Fri for 5 weeks (i.e. continuously with Notes: 1. Pretreatment investigations Baseline FBC U&Es and creatinine clearance (Cockcroft and Gault ) LFTs CEA ECG should be considered if previous history of angina, MI or arrhythmias If creatinine clearance (Cockcroft and Gault) is borderline, or for patients at extremes of weight, formal measurement e.g. EDTA should be requested. Weekly Toxicity assessment FBC U&Es and creatinine clearance (Cockcroft and Gault ) If creatinine clearance (Cockcroft and Gault) is borderline, or for patients at extremes of weight, formal measurement e.g. EDTA should be requested. REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 1 of 8

2 2. The Consultant must be made aware of any patient with abnormal blood chemistry or CEA at any stage of treatment 3. Following a toxicity assessment, treatment may be given if: Neutrophils 1.5 x 10 9 /l Platelets 75 x 10 9 /L If the above parameters are not the patient must be seen by the consultant prior to the next cycle. In addition patients reporting unexpected toxicities, adverse events or a neutropenic episode since the previous cycle will be scheduled to see medical staff within the chemotherapy clinic for dose review 4. Patients from Burton In view of these patients attending DHFT to receive their radiotherapy and the need for weekly blood tests, consideration should be given to assessing and managing patients referred from Burton within the DHFT chemotherapy service during radiotherapy planning and concurrent chemo-radiotherapy in order to minimise patient inconvenience. Any side effects or dose reductions must be communicated to the chemotherapy team in Burton, so that the adjuvant phase of treatment can be managed in Burton taking into account any toxicities experienced during this period. It is the responsibility of the patient s CONSULTANT in Derby to provide this information to Burton 5. Patients requiring chronic use of full dose oral or parenteral anticoagulants, high dose aspirin (>325mg/day), antiplatelet drugs or those patients with a known bleeding diathesis should receive capecitabine only if deemed by the Consultant to be in their best interest compared to other treatment options. (low dose aspirin is acceptable) 6. Patients with clinically significant cardiovascular disease [i.e. active; or < 12 months since e.g. cerebrovascular accident, myocardial infarction, unstable angina, New York Heart Association (NYHA) grade II or greatercongestive heart failure, serious cardiac arrhythmia requiring medication; or uncontrolled hypertension] should receive capecitabine only if deemed by the Consultant to be in their best interest compared to other treatment options REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 2 of 8

3 7. Dose Banding Capecitabine dose = 900 mg/m 2 12-hourly Number of tablets to be taken at each dose (morning & evening) Mon-Fri BSA (m 2 ) TWICE daily dose (mg) 150mg 500mg < > % dose reduction Capecitabine dose = 675 mg/m 2 12-hourly Number of tablets to be taken at each dose (morning & evening) Mon-Fri BSA (m 2 ) TWICE daily dose (mg) 150mg 500mg < > Capecitabine should commence on the morning of the first dose of radiotherapy. 9. There will be no capecitabine treatment on Saturdays or Sundays 10. If patients have swallowing difficulties, it is possible to dissolve the tablets in approx. 200ml of lukewarm water. There is no stability data, so this should be done immediately prior to use and the solution swallowed immediately, rinsing to ensure all of the dose has been ingested. The solution has a bitter taste and may be flavoured with a fruit juice or squash (except grapefruit juice) 11. Diarrhoea is more common and may be treated with Codeine Phosphate 30mg- 60mg qds prn. Loperamide may be added in if required 12. Patients having concurrent radiotherapy should have their Hb maintained above 10 g/dl. If Hb falls below 10 g/dl medical staff should be consulted to arrange a transfusion. REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 3 of 8

4 13. Dose Modifications for Toxicities When a dose reduction is made for the development of grade 2 (lasting >24hrs) or grade 3 toxicity this modification remains in place for the remainder of the planned chemo-radiotherapy. Haematological Toxicity Grade Toxicity Radiotherapy Capecitabine 1 ANC < LLN x 10 9 /L Continue 100% Platelets < LLN - 75 x 10 9 /L 2 ANC < x 10 9 /L PERFORM 2 x Weekly FBC Continue 100% Platelets <75-50 x 10 9 /L PERFORM 2 x Weekly FBC 3 ANC < x 10 9 /L 4 ANC Platelets Platelets <50-25 x 10 9 /L Neutropenic sepsis combined with grade 3 or 4 diarrhoea Continue Discontinue permanently Discontinue permanently Then 100% Then 75% Then 75% Palmar plantar syndrome Grade Toxicity Capecitabine 1 Minimal skin changes or dermatitis (e.g. erythema, Continue oedema or hyperkeratosis) without pain 2 Skin changes (e.g. peeling, blisters, bleeding, oedema, or hyperkeratosis) with pain; limiting instrumental activities of daily living (ADL) 3 Severe skin changes (e.g. peeling, blisters, bleeding, oedema, or hyperkeratosis) with pain; limiting self care ADL Interrput until 0-1, then resume at 75% Interrput until 0-1, then resume at 75% REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 4 of 8

5 Renal impairment CrCl (Cockroft-Gault or EDTA) Capecitabine > 50 ml/min Continue ml/min 75% dose < 30 ml/min Stop Cockcroft Gault Formula Females: 1.04 x (140 age) x weight (kg) serum creatinine (micromol/l) Males: 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. BMI= Weight(kg) Height(m) 2 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 is required, 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. Consider formal measurement of GFR for cachectic patients, where the serum creatinine may be low due to reduced muscle mass. REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 5 of 8

6 Diarrhoea Grade Toxicity Radiotherapy Capecitabine 1 Increase of <4 stools per day over Continue 100% baseline; mild increase in ostomy output compared to baseline 2 Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline Moderate cramping < 12 hours duration Continue 3 Increase of 7 stools per day over baseline; severe increase in ostomy output compared to baseline; limiting self care ADL; Sever cramping or peritonism (localised guarding of abdominal examination) 4 Life threatening consequences; urgent intervention required >12hrs duration 1 then resume 1 then resume REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 6 of 8 Omit evening dose at onset and reassess 24 hours later if <12hrs duration continue 1 then 75% 1 then 75% If neutropenic sepsis stop permanently Discontinue treatment permanently Deranged hepatic function and grade 3 fatigue and vomiting Grade Toxicity Radiotherapy Capecitabine 2 Elevated bilirubin > x Continue 75% ULN 3 Elevated bilirubin > x ULN Continue Stop ALT or AST > 3x ULN Continue Stop 4 Fatugue, vomiting or lethargy Interrupt until grade 0-1 Interrupt until grade 0-1 then 75% Mucositis & Stomatitis Grade Radiotherapy Capecitabine 1 Continue 100% 2 Continue then 75% 3 Continue but treat with appropriate supportive therapy then 75% 4 Discontinue treatment permanently 14. When an unplanned break in radiotherapy occurs (bank holiday, machine breakdown) capecitabine should be interrupted for that day and then resumed on the next planned day of radiotherapy

7 15. If a dose of capecitabine is omitted in error, no additional doses should be taken References: 1. NICE Technology Appraisal No. 100, Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes C) colon cancer; Issue date: April ARISTOTLE trial; protocol FINAL v th August 2010 REVIEWED BY C.WARD AUTHORISED BY: Dr R Kulkarni & PAGE 7 of 8