Phase I and Pharmacologic Study of Weekly Bolus Topotecan for Advanced Non–Small-Cell Lung Cancer

Purpose We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non–small-cell lung cancer. Patients and Methods Twelve patients with stage IIIB or IV disease were treated with topotecan by 30-minute intravenous infusion on days 1, 8, and 15 every 4 weeks. The dose was escalated in 2-mg/m 2 increments from the starting dose of 4 mg/m 2 until the MTD was reached. After the MTD had been reached in previously treated patients, chemotherapy-naive patients were enrolled for treatment at that dose, and the dose was escalated to estimate the MTD in the treatment-naive group. Results The MTD of topotecan was determined to be 6 mg/m 2 in the previously treated group and 8 mg/m 2 in the chemotherapy-naive group. All 3 previously treated patients experienced DLT at the 6-mg/m 2 dose level. Although only 1 of the 3 previously treated patients experienced DLT (grade 4 neutropenia for ≥ 3 days) at the 8-mg/m 2 dose level, skipping the topotecan dose on day 15 because of neutropenia was reported in 2 patients. Anorexia and general fatigue were the common nonhematologic toxicities. Conclusion The recommended dose of topotecan for phase II studies in previously untreated patients is 6 mg/m 2 on days 1, 8, and 15, every 28 days, and 4 mg/m 2 appears to be a suitable dose for use in previously treated patients with this schedule.