Phase I clinical and pharmacologic study of a 2-weekly administration of cisplatin and gemcitabine in patients with advanced non-small cell lung cancer.

Abstract

Our objective was to study the feasibility of schedule- and dose-intensive cisplatin plus gemcitabine in patients with non-small cell lung cancer (NSCLC) when given on 1 day in four 2-weekly cycles. Cisplatin was administered as a 3 h i.v. infusion followed by gemcitabine as a 30-min i.v. infusion on the same day, every 2 weeks. An interval of 1 h between the two infusions was applied. Patients received four courses without any break. An interpatient dose-escalation scheme was used. The starting dose was 87.5 mg/m of cisplatin and 1350 mg/m of gemcitabine. The pharmacokinetics of cisplatin and gemcitabine were determined in plasma and white blood cells. In total, 23 patients were included in the study. Median age of the patients was 56 years (range 27-76) and most patients were in good clinical condition. Thirteen patients received all planned courses. Dose-limiting toxicity was Common Toxicity Criteria grade 2 ototoxicity. The maximum tolerated dose was established at cisplatin 90 mg/m in combination with gemcitabine 1500 mg/m. This short induction schedule is practical and convenient for the patient. We conclude that the combination of cisplatin at a dose intensity of 51 mg/m/week followed by gemcitabine (1500 mg/m) on the same day is clinically feasible in NSCLC patients when given as a 2-weekly cycle.