Phase I Evaluation of Docetaxel and Topotecan for Patients with Advanced Solid Tumors

BACKGROUND. The authors administered a combination of docetaxel and topotecan with granulocyte-colony-stimulating factor (G-CSF) support in a Phase I study to define the maximum tolerated dose (MTD) of this regimen. METHODS. Patients with advanced-stage solid tumors were eligible for this trial if they had a Zubrod performance status of ≤ 2 and normal renal, hepatic, and bone marrow function. No previous therapy with taxanes or topoisomerase inhibitors was allowed. The authors administered both docetaxel and topotecan in a dose-escalated manner until the MTD was reached. Docetaxel was given on Day 1 of each cycle before topotecan, which was administered intravenously on Days 1-3. Granulocyte-colony-stimulating factor (G-CSF) support with 5 μg/kg subcutaneous injections was initiated on Day 4 and continued until the absolute granulocyte count recovered to 2000/μL. Treatment cycles were repeated every 21 days. RESULTS. Of the 11 patients enrolled in the current study, all were evaluable for toxicity and 10 were evaluable for response. A median of three treatment cycles was received (range, one to nine treatment cycles). The dose-limiting toxicity was Grade 4 (according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 2.0]). neutropenia with fever. The MTD was 75 mg/m² of docetaxel on Day 1 and 1.4 mg/m2 of topotecan on Days 1-3. There was one complete response and one partial response in patients with nasopharyngeal carcinoma and one partial response in a patient with small cell lung carcinoma (SCLC). The response durations were 24 weeks, 29 weeks, and ≥ 244 weeks, respectively. At the time of last follow-up, both patients with nasopharyngeal carcinoma were still alive at 241 weeks and 244 weeks, respectively. CONCLUSIONS. This trial demonstrated that a regimen of docetaxel and topotecan with G-CSF support was generally well tolerated and had promising activity in patients with nasopharyngeal and SCLC.