The efficacy and relationship between peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in Chinese patients with advanced non-small-cell lung cancer

摘要

To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.