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

To investigate the efficacy and relationship between plasma concentrations at the end of infusion (C _{end of infusion}) and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).

Patients were given gemcitabine by 120 min infusion [at a fixed dose rate (FDR) of 10 mg/m²/min] on days 1 and 8 of a 21-day cycle, immediately followed by carboplatin AUC 5 by 4 h infusion on day 1. C _{end of infusion} of gemcitabine was determined by ion-pair reversed-phase high-performance liquid chromatography (HPLC).

By the close-out date, in our study population, the estimated median time to tumor progression (TTP) was 7 months (95% CI 4–10 months), median overall survival (OS) was 12 months (95% CI 11.2–12.8 months). The mean value of C _{end of infusion} of 21 eligible patients was 16.48 ± 8.07 μmol/l (range 27.43–2.87 μmol/l). 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 C _{end of infusion} of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r ² = 0.4575; p < 0.05). A significant correlation (r ² = 0.5671; p < 0.05) was also observed between the percentage of reduction of PLTC and C _{end of infusion} of gemcitabine infusion.

The clinical data in this trial supports the further evaluation the regimen in advanced NSCLC patients, due to its predictable kinetic behavior and less severe toxicity profile than expected.