Prolonged gemcitabine infusion in advanced non-small cell lung carcinoma: A randomized Phase II study of two different schedules in combination with cisplatin

BACKGROUND. Preclinical and clinical evidence suggests that a fixed infusion rate of 10 mg/m² per minute may be more effective than the standard 30-minute infusion of gemcitabine. To investigate the activity and toxicity of the cisplatin plus gemcitabine combination with gemcitabine at a fixed infusion rate in patients with advanced non-small cell lung carcinoma (NSCLC), the authors conducted a randomized Phase II trial of cisplatin plus gemcitabine at the 30-minute standard infusion (calibration arm) or cisplatin plus gemcitabine at a fixed infusion rate (experimental arm), METHODS. A total of 112 chemonaive patients with advanced NSCLC entered the study: 57 patients in Arm A and 55 patients in Arm B. The patients were randomly assigned to receive gemcitabine at a dose of 1000 mg/m² on Days 1, 8, and 15 over 30 minutes (Arm A) or at a rate of 10 mg/m² per minute (Arm B). In both treatment arms, cisplatin at a dose of 80 mg/m² was administered on Day 15 every 28 days. RESULTS. The overall response rates in Arms A and B were 26% (95% confidence interval [95% CI], 10-42%) and 34% (95% CI, 17-52%) (intent-to-treat-analysis), respectively. The median time to disease progression was 6 months (range, 1-26 months) and 8 months (range, 2-21 months), respectively, for Arms A and B and the median overall survival was 13 months (range, 2-26 months) for each arm. It is interesting to note that a high response rate (67%) of brain metastases was noted in the experimental arm. Toxicity was tolerable and comparable in the two arms. CONCLUSIONS. The results of this randomized Phase II trial demonstrated that cisplatin plus gemcitabine with gemcitabine at fixed infusion rate (10 mg/m² per minute) is active and well tolerated in patients with advanced NSCLC.