Pemetrexed Combined with Oxaliplatin or Carboplatin as First-Line Treatment in Advanced Non–Small Cell Lung Cancer: A Multicenter, Randomized, Phase II Trial

Purpose: To determine efficacy and toxicity of two pemetrexed-based regimens in chemonaive patients with locally advanced or metastatic non–small cell lung cancer. Experimental Design: Patients were randomly assigned to receive pemetrexed 500 mg/m2 plus oxaliplatin 120 mg/m2 (PemOx) or pemetrexed plus carboplatin AUC6 (PemCb). All drugs were given on day 1 of a 21-day cycle for up to six cycles. Folic acid and vitamin B12 were given to all patients to minimize pemetrexed-related toxicities. Results: Forty-one patients received PemOx and 39 received PemCb. Objective tumor response rates were 26.8% for PemOx patients (95% confidence interval, 14.2-42.9) and 31.6% for PemCb patients (95% confidence interval, 17.5-48.7). Median time to progression was 5.5 and 5.7 months, respectively, for PemOx and PemCb. Median overall survival times were 10.5 months for both treatment groups (range, 20 months). The 1-year survival rate was 49.9% for PemOx patients and 43.9% for PemCb patients. Common toxicity criteria grade 3 or 4 hematologic toxicities among PemOx patients were grade 3 or 4 neutropenia (7.3%), grade 3 thrombocytopenia (2.4%), and grade 3 anemia (2.4%). PemCb patients experienced grade 3 or 4 neutropenia (25.6%), grade 3 or 4 thrombocytopenia (17.9%), and grade 3 anemia (7.7%). Grade 3 vomiting occurred in three PemOx patients and grade 3 fatigue occurred in three PemCb patients. One grade 3 neurosensory toxicity occurred in the PemOx group. Three patients (PemOx 1 and PemCb 2) experienced febrile neutropenia. Conclusions: Efficacy measures for both regimens seem similar to the most effective chemotherapies for advanced non–small cell lung cancer (platinum combinations) with less hematologic and nonhematologic toxicity. Comparing either of these two regimens to platinum-based therapies in a large randomized trial is warranted.