The optimal duration of vitamin supplementation prior to the first dose of pemetrexed in patients with non-small-cell lung cancer

Although folic acid and vitamin B12 supplements are recommended during pemetrexed therapy, the optimal duration for supplementation prior to the first dose of pemetrexed has not been defined. We analyzed adverse events during the first cycle of pemetrexed therapy in 350 patients with advanced non-small-cell lung cancer (NSCLC) who had received pemetrexed monotherapy. Patients were divided into two groups: group A and group B included patients who started vitamin supplements 5-14 days versus within 4 days before the first dose of pemetrexed, respectively. Groups A and B included 294 (84.0%) and 56 (16.0%) patients, respectively. The median number of cycles of pemetrexed was three in both groups. Patients in group A and B showed similar rates of leukopenia (6.1% vs. 5.4%, respectively, P=1.00), neutropenia (5.1% vs. 3.6%, P=1.00), thrombocytopenia (3.1% vs. 7.1%, P=0.14), neutropenic fever (0.7% vs. 0%, P=1.00), fatigue (20.1% vs. 19.6%, P=0.94), and anorexia (15.0% vs. 21.4%, P=0.23) during the first cycle of pemetrexed therapy. There were no significant differences in terms of hospitalization (4.4% vs. 5.4%, P=0.73) or unscheduled visits due to pemetrexed-related adverse events (8.2% vs. 12.5%, P=0.31) between groups A and B, respectively. Multivariate logistic regression analysis demonstrated that an age of ≥65 years (odds ratio, 3.49; 95% CI 1.12-10.86) and poor performance status (odds ratio, 3.96; 95% CI 1.12-14.03) were statistically significant predictive factors for grade 3 or 4 hematologic toxicity. The duration of vitamin supplementation before the first dose of pemetrexed did not affect the development of pemetrexed-related toxicities, suggesting that the initiation of pemetrexed-based chemotherapy does not have to be delayed to accommodate a vitamin supplementation schedule.