Paclitaxel and gemcitabine combination in a biweekly schedule in patients with advanced non small-cell lung cancer: a phase i study

Purpose: This phase I study was designed to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of the paclitaxel–gemcitabine combination in a biweekly schedule in chemotherapy-naive patients with advanced non small-cell lung cancer (NSCLC). Patients and methods: Treatment was administered on an outpatient basis every 2 weeks: paclitaxel over a 1-h IV infusion and gemcitabine as a 30-min IV infusion immediately following paclitaxel. Results: Twenty-nine patients were treated at six different dose levels, ranging from paclitaxel 135–175 mg/m² and gemcitabine 1,500–3,000 mg/m². A total of 198 cycles were administered (median 7, range 1–13). DLTs in the first two cycles were grade 4 neutropenia and myocardial ischemia at the dose level paclitaxel/gemcitabine 150/2,000 mg/m², febrile neutropenia and grade 4 neutropenia at the dose level paclitaxel/gemcitabine 175/2,500 mg/m², fatal pneumonitis, sudden death and grade 3 neutropenia at the dose level paclitaxel/gemcitabine 175/3,000 mg/m². The MTD was paclitaxel 175 mg/m² and gemcitabine 2,500 mg/m². The average dose intensity at this dose level was 98%. The overall intent-to-treat response rate was 35.7% (95% confidence interval CI] 17.97% - 53.47%). Overall median survival was 36 weeks (95% CI, 24-48). Conclusion: Paclitaxel and gemcitabine can be safely administered at a high dose intensity on an every-other-week schedule. The recommended phase II dose is paclitaxel 175 mg/m² and gemcitabine 2,500 mg/m².