Phase I/II study of gemcitabine and vinorelbine plus cisplatin in non-small cell lung cancer.

PURPOSE

We determine the maximum tolerated dose (MTD) and efficacy of gemcitabine plus vinorelbine combined with cisplatin in patients with non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Chemo naive patients with stage IIIA to IV non-small cell lung cancer received outpatient administration of gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 intravenously on days 1 and 8 every 21 days. Doses of gemcitabine and vinorelbine were escalated by 250 mg/m2 and 5 mg/m2, respectively, at each dose level. Cisplatin was administered at a fixed dose of 50 mg/m2 on days 2 and 9. After the MTD was reached, the study was continued as a phase II trial.

RESULTS

From January 1998 to March 1999, sixty-five patients were enrolled. The first 38 patients participated in the phase I evaluation. After 130 cycles, the dose-limiting toxicities were neutropenia, stomatitis, asthenia, and hepatotoxicity occurring at the third and fourth dose levels (doses of gemcitabine/vinorelbine of 1,500/25 and 1,000/30 mg/m2). For the subsequent phase II evaluation, 27 additional patients, out of a total of 53, receiving the MTD of gemcitabine and vinorelbine (1000-1250/25 mg/m2) followed (24 hours later) by cisplatin 50 mg/m2. Thirty one (58%) of 53 assessable patients responded. Objective response for patients with stages III and IV disease, respectively, were 65% and 47%. The median time to progression and the overall survival time were 9 months (95% CI: 5-12) and 11 months (95% CI: 9-13), respectively. World Health Organization toxicity > or = grade 3 neutropenia was registered in 28 (54%) of 52 assessable patients (2% with febrile neutropenia), and > or = grade 3 thrombocytopenia in 15 (29%) patients (4% with bleeding). Nausea/vomiting (> or = grade 2) and asthenia (moderate to severe) occurred in 24 (46%) and 14 (27%) patients, respectively.

CONCLUSION

Gemcitabine 1,000-1,250 mg/m2 plus vinorelbine 25 mg/m2 on days 1 and 8, followed by cisplatin 50 mg/m2 24 hours later, is safe for outpatient administration and active in patients with NSCLC.