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A Dose-Escalation Study of Weekly Topotecan, Cisplatin, and Gemcitabine Front-Line Therapy in Patients with Inoperable Non-Small Cell Lung Cancer

^a Medical Oncology Hematology Consultants, PA, Christiana Care Health System, Helen F. Graham Cancer Center, Wilmington, Delaware, USA; ^b GlaxoSmithKline, Philadelphia, Pennsylvania, USA; ^c Virtua Memorial Hospital, Mt. Holly, New Jersey, USA

Correspondence: Michael J. Guarino, M.D., Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, Suite 2200, Newark, Delaware 19713, USA. Telephone: 302-366-1200; Fax: 302-366-1700; e-mail: mguarino{at}magpage.com

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/m²), cisplatin (20 mg/m²), and gemcitabine (1,000 mg/m²) 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/m².

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/m² 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/m² days 1, 8, 15), cisplatin (20 mg/m² days 1, 8, 15), and gemcitabine (1,000 mg/m² 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.

Key Words. Cisplatin • Dose escalation • Gemcitabine • Maximum-tolerated dose • Non-small cell lung cancer • Topotecan

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				D. J. Stewart Update on the Role of Topotecan in the Treatment of Non-Small Cell Lung Cancer Oncologist, December 1, 2004; 9(suppl_6): 43 - 52. [Abstract] [Full Text] [PDF]