Phase I Trial of Topotecan in Combination with Gemcitabine in Refractory Solid Tumor Patients

Purpose: To determine maximum tolerated dose (MTD) and evidence of antitumor activity of topotecan in combination with gemcitabine in refractory cancer patients. Methods: This was a Phase I, prospective, dose-escalation trial that employed a novel-dosing schema to investigate clinical safety. Patients were treated in six cohorts with topotecan (T) + gemcitabine (G). The doses of T and G were administered by 30-minute IV infusion, T on days one through five (0.3 mg/m2 to 1 mg/m2) and G on days one and 15 of a 28-day cycle (1000 mg/m2 to 1500 mg/m2). Toxicity was monitored. Results: Twenty-three cancer patients were enrolled (colorectal, n = 5; lung, n = 4; gastric, n = 4; esophageal, n = 2; other, n = 8). Two of three patients developed grade 3 nonhematologic toxicity attributed to study regimen, thereby fulfilling dose limiting toxicity requirements at cohort 6 (T, 1 mg/m2, G, 1500 mg/m2). Maximum tolerated dose (MTD) was established at cohort 5 (T, 1 mg/m2, G, 1250 mg/m2). Ten patients were treated at co...