West of Scotland Cancer Network Chemotherapy Protocol. Cisplatin and Pemetrexed for Malignant Mesothelioma (LUWOS 0021)

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1 West of Scotland Cancer Network Chemotherapy Protocol Cisplatin and Pemetrexed for Malignant Mesothelioma (LUWOS 0021) Indication Palliative chemotherapy for malignant mesothelioma of the pleura Eligibility criteria Confirmed diagnosis of malignant mesothelioma of the pleura Performance status 0-1 Treatment intent Palliative Pre-treatment evaluation Informed consent, provision of verbal and written information Assessment of performance status Chest X-ray CT chest and upper abdomen Height, weight and BSA Baseline investigations FBC, U&E, LFTs Assessment of renal function use Cockcroft-Gault equation to calculate creatinine clearance. If creatinine clearance <60ml/min consider EDTA/24hr collection. Supportive therapy Pre treatment Folic acid 400micrograms/day oral tablet to start at least 1 week before treatment with cisplatin and pemetrexed and continue for 21 days after the last dose of pemetrexed Vitamin B micrograms IM every 9 weeks to start the week preceding the first dose of pemetrexed Prophylaxis for skin rash - dexamethasone 4 mg orally twice daily for 5 days beginning the day before chemotherapy (D1-3 for rash as per SPC, D 4-5 as antiemetic). Page 1 of 5

2 Post treatment Antiemetics as per local policy (no TTO antiemetic dexamethasone see above, skin rash) GCSF prophylaxis is not recommended consider dose reduction instead Regime Drug Dose Route Administration Day to be given Pemetrexed 500mg/m 2 IVI Infusion over 10 D1 mins in 100ml NaCl 0.9% Cisplatin 75mg/m 2 IVI Infusion over 4 hrs D1 in 1L NaCl 0.9% 30 mins after completion of pemetrexed Maximum cumulative dose N/A N/A Pre and post-hydration is required. Refer to local policy. Repeat every 21 days for up to 4 cycles. Stop if disease progression or unable to tolerate treatment. Emetogenic risk: High refer to local antiemetic policy Adverse effects Common Uncommon Cisplatin nephrotoxicity, nausea and vomiting, ototoxicity, myelosuppression, neuropathy, electrolyte disturbances, fatigue. Pemetrexed chest pain, fatigue, rash, nausea and vomiting, constipation, myelosuppression, increased creatinine, dyspnoea. Cisplatin alopecia, allergic reaction. Pemetrexed renal failure, allergic reaction, thrombosis/embolism. For more detailed information regarding the above please refer to the full SPC. Extravasation risk category Drug Cisplatin Pemetrexed Category Exfoliant Non-vesicant Page 2 of 5

3 Precautions & contraindications Contraindicated in hypersensitivity to either drug or their excipients Caution in patients with impaired hepatic function Not recommended in severe renal impairment Avoid in pregnancy and breast feeding Contraceptive measures should be taken in women of child bearing age Males should be advised not to father a child during treatment and for up to 6 months after Drug interactions Cisplatin nephrotoxicity and ototoxicity may be exacerbated by treatment with other nephrotoxic/ototoxic drugs. Cisplatin may reduce phenytoin serum levels. Pemetrexed - Concurrent nonsteroidal anti-inflammatory agents should be stopped for 1 week before treatment and for 1 week after treatment as they may decrease renal clearance. Investigations prior to subsequent cycles FBC (Neut>1.5, Pl>100), U&E, LFTs performance status assessment of toxicity, documented by CTCAE version 3.0 Dose modifications Haematological Result Value Action Platelets x 10 9 /L <100 Delay one week Neutrophils < 1.5 Delay one week Neutropenic sepsis since previous cycle Renal Neutrophils < 1.0 and fever 38.5 C GFR % of full dose Comments Cisplatin % May dose reduce or D/W oncologist give over 2 days < 40mls/min Contraindicated D/W oncologist Pemetrexed 45ml/min Contraindicated D/W oncologist Discuss with consultant consider 25% dose reduction Page 3 of 5

4 Hepatic Drug Bilirubin AST/ALT % of full dose Cisplatin N/A N/A No dose reduction necessary Pemetrexed 1.5 x ULN 3 x ULN 5 X ULN if liver mets 100% Others Toxicity Grade Action Nausea and vomiting 1 or above Diarrhoea Any grade requiring hospitalisation and 3-4 Increase/change antiemetics. No dose reduction. Reduce both drugs to 75% of dose Usually mild and self-limiting. No routine prophylactic antidiarrhoeal medication is needed. Use loperamide if needed at standard dose. Mucositis 0-2 Give 100% of both drugs 3-4 Reduce pemetrexed dose to 50% Neurotoxicity % 2 100% pemetrexed; 50% cisplatin 3-4 D/W consultant Any other toxicity 3-4 Reduce both drugs to 75% of dose Evaluation of response to treatment Review by oncologist every cycle CT scan every 2 cycles References Vogelzang NJ, Rusthoven J, Paoletti P, et al. Phase III single-blinded study of pemetrexed +cisplatin vs. cisplatin alone in chemonaive patients with malignant pleural mesothelioma. Proc Am Soc Clin Oncol 2002; 21: abstr 5. Hughes A, Calvert P, Azzabi A, et al. Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in patients with malignant pleural mesothelioma. J Clin Oncol 2002;20: Thodtmann R, Depenbrock H, Dumez H, et al. Clinical and pharmacokinetic phase I study of multitargeted antifolate (LY231514) in combination with cisplatin. J Clin Oncol 1999;17: Drug Information Handbook for Oncology. Solimando DA, editor. 4 th edn. Lexi- Comp Ohio The Cytotoxics Handbook. Allwood M, Stanley A, Wright P eds. 4 th edn. Radcliffe Medical Press, Oxon Scottish Medicines Consortium advice Erlotinib No. 192/05, July 205. Page 4 of 5

5 Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update JCO 2006; 24 (18): Pemetrexed. Summary of Product Characteristics. Roche Products Limited Written by: David Dunlop, Fiona MacLean, Gillian Barmack Date prepared: November 2006 Approved by: WOS Lung MCN May 2006 Review date: May 2008 Page 5 of 5