Pemetrexed for the treatment of malignant pleural mesothelioma

Pemetrexed (Alimta, Eli Lilly and Company) is licensed, in combination with cisplatin, for the treatment of chemotherapy-naive patients with unresectable MPM. Pemetrexed is a multi-targeted folate antagonist that inhibits DNA replication. Cisplatin is a platinum-based chemotherapeutic agent that has anti-tumour activity, either as a single agent or in combination, for a number of different cancers. The licensed dose of pemetrexed is 500 mg/m² body surface area, to be administered as a 10-minute intravenous infusion on the first day of a 21-day cycle. It is followed approximately 30 minutes later by cisplatin (recommended dose 75 mg/m² body surface area) infused over 2 hours. In order to reduce toxicity, patients treated with pemetrexed must receive folic acid and vitamin B₁₂ supplementation. To reduce the incidence and severity of skin reactions, patients are pre-medicated with a corticosteroid.

Adverse effects commonly associated with pemetrexed include nausea, vomiting, fatigue and neutropenia. Skin rash, mucositis and liver function abnormalities have also been reported. Cisplatin causes nausea and vomiting in the majority of patients. This is controllable in 50–80% of patients with anti-emetic drugs. Serious toxic effects of cisplatin on the kidneys, bone marrow and ears are common, and serum electrolyte disturbances, hyperuricaemia, allergic reactions and cardiac abnormalities have also been reported. For full details of side effects and contraindications, see the summaries of product characteristics.

Pemetrexed costs £800 for a 500-mg vial (excluding VAT, 'British national formulary' [BNF]53rd edition). The cost per patient, assuming an average of five treatment cycles and a body surface area of 1.8 m², is approximately £8000. Costs may vary in different settings because of negotiated procurement discounts.