This randomized phase II trial evaluated single-agent pemetrexed or sequential pemetrexed/gemcitabine in patients with non-small cell lung cancer (NSCLC) who were elderly (> or = 70 years) or younger than 70 years and ineligible for platinum-based chemotherapy. Chemonaive patients with stage IIIB/IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 received either 500 mg/m2 of pemetrexed (day 1, every 3 weeks) for eight cycles, or the same dosage of pemetrexed for cycles 1 and 2 and then 1200 mg/m2 of gemcitabine (days 1 and 8, every 3 weeks) for cycles 3 and 4 (repeated once for a total of eight cycles). All patients were given vitamin B12 and folic acid supplementation. From July 2003 to July 2004, 87 patients (44 pemetrexed; 43 pemetrexed/gemcitabine) received treatment. The median time to progression was 4.5 (95% confidence interval: 3.0-9.3) and 4.1 months (95% confidence interval: 1.7-5.8) for the pemetrexed and pemetrexed/gemcitabine arms, respectively, and the median progression-free survival time was 3.3 months for both arms. Tumor response rates for the pemetrexed and pemetrexed/gemcitabine arms were 4.5% and 11.6%, respectively. The median overall survival time was 4.7 months for the pemetrexed arm and 5.4 months for the pemetrexed/gemcitabine arm, with respective 1-year survival rates of 28.5% and 28.1%. Grade 3/4 hematologic toxicity consisted of neutropenia (4.5% pemetrexed; 2.3% pemetrexed/gemcitabine), febrile neutropenia (4.5% pemetrexed; 4.7% pemetrexed/gemcitabine), thrombocytopenia (4.5% pemetrexed; 7.0% pemetrexed/gemcitabine), and anemia (6.8% pemetrexed; 4.7% pemetrexed/gemcitabine). No grade 3/4 nonhematologic toxicities exceeded 4.7% in either arm. Single-agent pemetrexed and sequential pemetrexed/gemcitabine have shown moderate activity and are well tolerated as first-line treatments for advanced NSCLC in elderly patients or patients unsuitable for platinum-based combination chemotherapy.
