Regimen: Gemcitabine-Capecitabine (GEMCAP) for Pancreatic Cancer

Transcription

1 Regimen: Gemcitabine-Capecitabine (GEMCAP) for Pancreatic Cancer Indication Regimen detail Administration First line palliative therapy for locally advanced or metastatic or relapsed disease Day Drug Dose Route 1, 8, 15 Gemcitabine 1,000mg/m 2 IV infusion 1 to 21 Capecitabine 830mg/m 2 twice daily for 21 days followed by 7 day rest Gemcitabine is administered as an IV infusion in mL sodium chloride 0.9% over 30 minutes. Capecitabine is available as 150mg and 500mg tablets. Tablets should be taken within 30 minutes after morning and evening meals. If vomiting occurs after a dose of capecitabine, a replacement dose should not be administered. oral Body Surface Area (m 2 ) Dose (mg) (Twice daily) Dose level 830mg/m 2 twice daily Number of 150mg tablets and/or 500mg tablets per administration 150mg 500mg morning, 1300 evening 1 morning, 2 evening Frequency Every 28 days until disease progression Extravasation Gemcitabine is neutral (Group 1) Premedication Emetogenicity Additional recommended supportive medication Pre-treatment evaluation Regular investigations N/A This regimen has low emetogenic potential refer to local protocol Give loperamide to all patients for the treatment of diarrhoea. Topical emollients may reduce the severity of palmar-plantar erythrodysaesthesia. H 2 antagonist or Proton Pump Inhibitor if required. FBC U+E LFT FBC U+E Pre Day 1 results valid for 72 hours Days 8 and 15 results valid for 24 hours Pre Day 1 results valid for 7 days (may be performed more frequently if clinically indicated) Controlled document Document Number Version Number Page 1 of 5

2 LFT Standard limits for administration to go ahead if blood results not within range, authorisation to administer must be given by prescriber/consultant Results valid for 7 days (may be performed more frequently if clinically indicated) Neutrophil count 1.0 x 10 9 /L Platelet count 100 x 10 9 /L Creatinine clearance Bilirubin 30mL/min 1.5 x ULN Dose modifications Haematological toxicity Renal impairment Hepatic impairment ANC (x 10 9 /L) Platelets (x 10 9 /L) Gemcitabine Capecitabine (Days 1, 8 15) (Day 1 only) 1.0 and > % dose 100% dose or * < 0.5 or < 50 Omit (D1 gem should be delay 1 week?) Delay 1week or until count recovery *This dose reduction is for the day of treatment only; dose can return to full dose after blood count recovery. CrCl (ml/min) Gemcitabine Dose Capecitabine Dose >50 100% 100% % (with close monitoring) < 30 Consider dose reduction - clinical decision Contra-indicated AST +/- ALT Bilirubin Capecitabine dose 2.5 x ULN and/or 3.0 x ULN 100% > 2.5 x ULN and/or > 3.0 x ULN Discuss with consultant. Current evidence suggests safe cape SPC recommends interruption of treatment Gemcitabine: there is limited information available on the use of gemcitabine in patients with hepatic impairment. It should, therefore, be used with caution. AST elevations do not appear to cause dose-limiting toxicities. NCI Common toxicity criteria If bilirubin > 1.5 x ULN, consider reducing dose to 800mg/m 2. Toxicity Definition Dose adjustment Febrile neutropenia (Gemcitabine) Palmar-Plantar Erythrodyaesthesia (Capecitabine) ANC<0.5 x 10 9 /L plus fever requiring IV antibiotics +/- hospitalisation Reduce dose of Gemcitabine by 25% 1 st appearance: delay until resolved to Grade 1 and then resume at 100% Grade 1 and then resume at Grade 1 and then resume at 50% 1 st appearance: delay until resolved to Grade 1 and then resume at Grade 1 and then resume at 50% Controlled document Document Number Version Number Page 2 of 5

3 Stomatitis/mucositis* resume at 100% Grade 1 and then resume capecitabine at, gemcitabine at 100% Diarrhoea* Grade 4 Grade 4 resume capecitabine at, gemcitabine at 100% Discontinue or delay until toxicity Grade 1, then resume both drugs at 50% resume at 100% Grade 1 and then resume capecitabine at, gemcitabine at 100% resume capecitabine at, gemcitabine at 100% Discontinue or delay until toxicity Grade 1, then resume both drugs at 50% Adverse effects the contents of the table indicate the adverse effects that should be documented on consent to treatment forms * Note that severe diarrhoea and/or severe mucositis early in the first treatment cycle can be the first presenting toxicity due to DPD enzyme deficiency. This can lead to potentially fatal neutropenia. Rare but serious side effects Interstitial Pneumonitis, ARDS Cardiotoxicity Hepatotoxicity Thrombosis/embolism Peripheral Neuropathy Other Frequently occurring side effects Myelosuppression Nausea and vomiting Fatigue/ asthenia Rash Mucositis and Stomatitis Diarrhoea Haematuria Palmar-plantar erythrodysaesthesia (PPE) / Hand-foot syndrome (HFS) Headache; anorexia; alopecia (mild); taste disturbances Controlled document Document Number Version Number Page 3 of 5

4 Significant drug interactions For full details consult product literature/reference texts Comments Cumulative Doses References Warfarin/coumarin anticoagulants: increased or fluctuating anticoagulant effects. Avoid if possible: in the first instance, consider switching patient to a low molecular weight heparin during treatment or if the patient continues taking an oral anticoagulant monitor the INR at least once a week and adjust dose accordingly. Gemcitabine is a radio-sensitiser Phenytoin and fosphenytoin: capecitabine may increase plasma concentrations of phenytoin and fosphenytoin. Patients taking phenytoin or fosphenytoin concomitantly with capecitabine should be regularly monitored for increased phenytoin plasma concentrations. Sorivudine and analogues: capecitabine must not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine. There must be at least a 4-week waiting period between end of treatment with sorivudine or its chemically related analogues and the start of capecitabine therapy. Allopurinol may decrease efficacy of capecitabine; concomitant use should be avoided. Folinic acid may enhance the toxicity of capecitabine; concomitant use should be avoided. Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe toxicity secondary to reduced fluorouracil metabolism avoid use of capecitabine in patients with known DPD deficiency Cardiotoxicity has been associated with fluoropyrimidine therapy, with adverse events being more common in patients with a prior history of coronary artery disease. Caution must be taken in patients with a history of significant cardiac disease, arrhythmias or angina pectoris. N/A Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol 1997; 15 (6): Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et al. Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol (33): Criteria for Adverse Events (CTCAE) version 4.03 [internet] accessed 25/01/2012 available at Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment [internet]. accessed 10/11/2011 available at %20Dosage%20adjustment%20for%20cytotoxics.doc Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in renal impairment [internet]. accessed 10/11/2011 available at %20Dosage%20adjustment%20for%20cytotoxics.doc Baxter K, editor. Stockley s Drug Interactions. Pharmaceutical Press; Accessed online on 06/05/09 available at Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4 th ed. Radcliffe Medical Press Summary of Product Characteristics Gemcitabine 200mg powder for solution for infusion, Gemcitabine 1g powder for solution for infusion, Gemcitabine 2g powder for solution for infusion (Hospira) [internet]. accessed 25/01/2012 available from Summary of Product Characteristics Xeloda (Capecitabine) 500mg and 150mg Tablets (Roche) [internet], accessed 25/01/2012 available from Controlled document Document Number Version Number Page 4 of 5

5 Document title Gemcitabine and Capecitabine (Pancreatic) Document number ASWCS12 GI026 Approval date 15/11/2012 Written by Stephen Falk, Consultant Clinical Oncologist BHOC Checked by Tariq White, Network Nurse Director, ASWCS Authorised by Jeremy Braybrooke, Chair ASWCS Drugs and Therapeutics Committee Review date 15/11/2013 Document reviewed by Version number 1.1.a Summary of changes Version Controlled document Document Number Version Number Page 5 of 5