Phase I/II study of gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results.
Steward WP., Dunlop DJ., Dabouis G., Lacroix H., Talbot D.
Sixty-six patients with advanced non-small cell lung cancer have been entered into a phase I/II study of a combination of gemcitabine and cisplatin. An initial phase I portion of the study has been completed, and 16 patients have been entered using a fixed dose of gemcitabine 1,000 mg/m2 as a 30-minute intravenous infusion weekly for 3 weeks. Cisplatin was administered on day 15 following gemcitabine with appropriate prehydration and posthydration. The study was designed to allow for sequential groups of three patients to receive three dose levels of cisplatin (60 mg/m2, 75 mg/ m2, and 100 mg/m2). Dose modification and patient numbers were to be increased at any dose level if significant toxicity was observed. The regimen was well tolerated at all doses, and the final level of cisplatin 100 mg/m2 was expanded to 10 patients before the phase II portion was opened. Neutropenia (World Health Organization grade 4 in three patients) and thrombocytopenia (grade 3 or 4 in five patients) were the main hematologic toxicities recorded. These episodes were brief and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients, but was no worse than would be expected from cisplatin alone. Alopecia, when it occurred, was minimal (no hair loss in 10 patients and grade 1 or 2 in six patients). No significant renal toxicity or neurotoxicity was seen. A phase II study with cisplatin 100 mg/m2 and gemcitabine 1,000 mg/m2 has been opened, and to date 43 patients are evaluable for response. Eighteen (42%) patients have achieved partial remissions. The study will close when 50 evaluable patients have been entered.