Administration of pemetrexed immediately following gemcitabine as front-line therapy in advanced non-small cell lung cancer: A phase II trial

Background: Pemetrexed and gemcitabine have demonstrated independent anti-tumor activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The combination of these two therapies may produce synergistic anti-tumor effects. Previous studies of this combination have included a 90-min separation between the two drugs. More recent preclinical studies have suggested that this delay in administration might be unnecessary. This phase II study was designed to determine the objective tumor response rate and toxicity when pemetrexed was administered immediately after gemcitabine on day 1. Methods: Chemonaïve patients stage IIIB with pleural effusion or stage IV NSCLC were enrolled. Treatment consisted of gemcitabine 1250 mg/m² (30-min intravenous infusion on days 1 and 8) and pemetrexed 500 mg/m² (10-min IV infusion, immediately following gemcitabine, on day 1) every 21 days. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results: The 53 enrolled patients completed a total of 199 cycles (median = 4.0, mean = 3.8). Best tumor response consisted of 1 complete response (2.0%), 15 partial responses (30.6%), 17 with stable disease (34.7%), and 16 with progressive disease (32.7%). Median time to disease progression was 3.3 months and median survival was 10.3 months. Grades 3/4 hematologic toxicities (% patients) consisted of: neutropenia (43.4), anemia (9.4), febrile neutropenia (7.5%) and thrombocytopenia (1.9). The most common grades 3 or 4 non-hematologic events were: dyspnea (15.1), fatigue (11.3), and pyrexia (9.4). One patient (1.9%) experienced grade 2 alopecia. Conclusion: This schedule of pemetrexed plus gemcitabine is tolerable and offered the advantage of not requiring a 90-min delay between the two drugs. Response rate, survival, time to disease progression, and toxicity were acceptable and similar to other NSCLC regimens.