A dose-escalation study of weekly topotecan, cisplatin, and gemcitabine front-line therapy in patients with inoperable non-small cell lung cancer.

Purpose: To determine the optimal dose of combination topotecan, cisplatin, and gemcitabine in advanced non-small cell lung cancer patients.

Materials And Methods: This single-center, single-practice, phase I trial enrolled chemotherapy-naïve patients with inoperable stage IIIB/IV disease. Initial treatment was topotecan (0.5-2.0 mg/m(2)), cisplatin (20 mg/m(2)), and gemcitabine (1,000 mg/m(2)) on days 1, 8, and 15 of a 28-day cycle. Dose-limiting thrombocytopenia at week 3 necessitated less frequent gemcitabine dosing (days 1 and 15 of each cycle). Thereafter, topotecan dose escalation proceeded to the target dose of 2 mg/m(2).

Results: Thirty patients were enrolled and evaluable for toxicity assessment. Treatment was extremely well tolerated: only one grade 4 adverse event (leukopenia); no hospitalizations for treatment-related toxicities; no fever/neutropenia. Although no dose-limiting toxicities developed, 1.75 mg/m(2) topotecan is considered optimal and recommended for further study because it was well tolerated, active, and did not require dose adjustments or delays in therapy. Eleven of 29 (38%) evaluable patients achieved a partial response. Median survival was 38 weeks (range 4-110 weeks), median progression-free survival was 17 weeks, and the 1-year survival rate was 33%. Two patients remain alive after 108-122 weeks of follow-up.

Conclusion: A 28-day cycle of topotecan (1.75 mg/m(2) days 1, 8, 15), cisplatin (20 mg/m(2) days 1, 8, 15), and gemcitabine (1,000 mg/m(2) days 1, 15) was a safe and well-tolerated outpatient treatment for advanced non-small cell lung cancer. The favorable preliminary efficacy and safety of this regimen suggest that further study in phase II trials, including quality-of-life end points, is warranted.