Pemetrexed in Relapsed Small-Cell Lung Cancer and the Impact of Shortened Vitamin Supplementation Lead-in Time Results of a Phase II Trial

Introduction: We undertook a phase II trial to assess the efficacy and safety of single-agent pemetrexed (P) in relapsed small-cell fun 9 cancer (SCLC) patients. Methods: Patients had limited- or extensive-stage SCLC performance status 0 to 2, and one prior chemotherapy regimen. Initial P dose was 500 mg/m(2) every 21 days. Planned sample sizes were 36 sensitive (S) patients in a two-stage sequential fashion with early stopping rule, and 25 refractory (R) patients in a single-stage design without stopping rule. Patients received folic acid and Vitamin B, prior to P, and B-12 could be given up until P treatment. Primary Outcome measure was response rate. Results: Enrollment occured from July 2004 to March 2006. The stopping rule was invoked when <3 of 14 S patients responded. The protocol was amended to evaluate P 900 mg/m(2) in cohorts of 40 S and 40 R patients. Overall, 121 patients were enrolled. with 116 patients treated. S (n = 53) and R (n = 63) patients were analyzed separately at both close levels, Across the 4 treatment groups (S500. S900, R500, R900), 1 patient (2.63%) in the S900 group had a partial response. Overall, 18 patients (16%) had stable disease. Eighty-seven patients (75%) had progressive disease. Responses were not evaluable in 10 patients (8.6%). Overall response rate was 0.9%. Across treatment groups, disease control rates (partial response + stable disease) were 20%, 15.8%, 21.7%, and 12.5%, respectively. Median time to progression ranged from 1.2 to 1.5 months. median survival times ranged from 2.5 to 6.1 months, and 1-year survival rates ranged from 5.6 to 25.8%. Common grade 3/4 hematologic toxicities (at 500 and 900 mg/m(2)) were neutropenia (16%; 9%) and leukopenia (11%: 8%). and nonhematologic toxicities were dyspnea (11%; 10%) and failure (16%; 9%). Retrospective analysis of cycle 1 events by timing of B, administration showed no trend toward more frequent serious toxicities when 13, Was given <7 days prior to P. Conclusions: Single-agent P 500 mg/m(2) shows minimal activity in relapsed SCLC patients. P can be given at 900 mg/m(2) without significant increase in serious toxicities, but does not seem to increase efficacy. B,, given <7 days before P does not seem to be associated with increased serious toxicities.