P1-229: The impact of shortened vitamin supplementation lead-in time before pemetrexed (P) in patients with relapsed small-cell lung cancer (SCLC)

Clinical studies of P have shown less overall toxicity and reductions in Grades 3/4 hematologic and nonhematologic toxicities when pts are pretreated with folic acid and Vitamin B12. Current recommendations are to give folic acid 350 μg to 1000 μg by mouth for at least 5 of 7 days prior to the 1st dose of P, and 1 injection of Vitamin B12 1000 μg during the week preceding the 1st P dose. Treatment delay to allow this supplementation may be clinically undesirable, particularly in pts with aggressive malignancies. A trial evaluating single-agent P for the treatment of relapsed SCLC gave us opportunity to observe the effects of a shortened lead-in time for vitamin supplementation. We reviewed data from a US trial designed to assess the safety and efficacy of single-agent P in chemosensitive and chemorefractory relapsed SCLC pts. Eligible pts had limited or extensive-stage SCLC, PS 0 to 2, and 1 prior chemo regimen. Pts received P doses of 500 mg/m2 or 900 mg/m2 q 21 d. The protocol required the administration of folic acid for at least 5 of 7 days prior to the 1st P dose, and Vitamin B12 administration on Day 1, Cycle 1, or up to 14 days prior to the 1st P dose. Adverse events were tabulated using Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) terminology. Included in the analysis were pts who received at least 1 dose of folic acid prior to 1st P dose. We analyzed preliminary toxicity results for pts receiving Vitamin B12 for 0-3, 4-6 and ≥7 days prior to 1st P dose. From 7/04 to 3/06, 116 pts were treated with P. M/F 57/59; median age 64.5 (range 35-85); PS 0/1/2 39/57/20. Because toxicities observed between the two P doses were not significantly different, the combined toxicities for both dosing groups are reported in the table. B12 given less than 7 days prior to P does not appear to be associated with increased serious toxicities.