Pemetrexed

? Pemetrexed inhibits several folate-dependent enzymes, thereby inhibiting both thymidine synthesis and purine nucleotide synthesis. ? The median survival time of patients with NSCLC treated with pemetrexed 500 mg/m² monotherapy every 21 days versus docetaxel 75 mg/m² every 21 days in a second-line setting was 8.3 and 7.9 months (hazard ratio = 0.99, 95% CI 0.82-1.20, with a preset 95% CI upper limit of <1.11) in a phase III randomized, nonblind, multicenter trial (n = 571). In a phase III randomized, single-blind, multicenter trial (n = 448) in chemotherapy-naive patients with malignant pleural mesothelioma (MPM), pemetrexed 500 mg/m² plus cisplatin 75 mg/m² every 21 days was better in terms of median survival time (12.1 vs 9.3 months; hazard ratio 0.77, p < 0.05) and tumor response rates (41.3% vs 16.7%, p < 0.001) than cisplatin 75 mg/m² every 21 days. ? During the MPM trial, a protocol change required all patients to receive supplementation with oral folic acid daily and intravenous cyanocobalamin once every 9 weeks (i.e. supplementation) because of pemetrexed toxicity. ? Pemetrexed was generally well tolerated as monotherapy in patients with advanced NSCLC and as combination therapy in patients with MPM if supplemented. In patients with NSCLC, neutropenia, alopecia, and fatigue were the most common adverse events, whereas in patients with MPM they were neutropenia, leukopenia, nausea, and vomiting. Severe toxicities in pemetrexed recipients in the NSCLC trial were infrequent.