Pemetrexed as second-line treatment in malignant pleural mesothelioma after platinum-based first-line treatment

Introduction: Pemetrexed is active as first-line treatment of malignant pleural mesothelioma. The objective was to evaluate its activity as second-line treatment. Methods: Patients had disease progression of malignant pleural mesothelioma after previous platinum-based regimens without pemetrexed. Treatment was pemetrexed alone or pemetrexed combined with carboplatin. Pemetrexed dosing was 500 mg/m(2) and carboplatin was AUC (area under the curve) 5 once every 3 weeks. Results: Thirty-nine patients were included: 28 Danish patients received pemetrexed (three patients received pemetrexed as third-line treatment), whereas 11 Norwegian patients received pemetrexed plus carboplatin. Most patients were men (90%), had epithelial subtype (85%), and International Mesothelioma Interest Group stages III to IV (77%). Median age was 62 years (range, 30-77). The median number of treatment courses was six (range, 1-23). Common Toxicity Criteria grade 3 to 4 toxicity occurred only with respect to leukocytopenia (pemetrexed: 14% of patients; pemetrexed plus carboplatin: 9%) and thrombocytopenia (pemetrexed: 7%; pemetrexed plus carboplatin: 18%). One patient receiving pemetrexed died of sepsis. Partial response rates were 21% and 18%, the median time to progression was 21 weeks (range, 4-92) and 32 weeks (range, 4-128+), and the median survival was 42 weeks (range, 4-99) and 39 weeks (range, 10-128+) with pemetrexed and pemetrexed plus carboplatin, respectively. Conclusions: Pemetrexed was generally well tolerated with noteworthy activity in malignant pleural mesothelioma after previous platinum-based treatment and may be considered for second-line treatment.