A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300-700 mg/ m(2)) and vinorelbine (days 1 and 8, 15-30 mg/m(2)) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B-12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700mg/m(2) and vinorelbine 30mg/m(2); and recommended phase II dose was pemetrexed 500mg/m(2) and vinorelbine 30 mg/m(2). When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), white prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved.