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

2008; Elsevier BV; Volume: 3; Issue: 11 Linguagem: Inglês

10.1097/jto.0b013e3181898e32

1556-1380

Mark A. Socinski, Robert N. Raju, Marcus A. Neubauer, David A. Smith, Donald Richards, Michael A. Savin, Robert L. Ruxer, Craig H. Reynolds, Feng Zhan, Jane Bromund, Ruqin Chen, Coleman K. Obasaju,

Neuroendocrine Tumor Research Advances

Introduction We undertook a phase II trial to assess the efficacy and safety of single-agent pemetrexed (P) in relapsed small-cell lung 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 12 prior to P, and B 12 could be given up until P treatment. Primary outcome measure was response rate. Results Enrollment occurred 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 dose 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 fatigue (16%; 9%). Retrospective analysis of cycle 1 events by timing of B 12 administration showed no trend toward more frequent serious toxicities when B 12 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 12 given <7 days before P does not seem to be associated with increased serious toxicities.