Phase I trial of weekly topotecan and gemcitabine in patients with solid tumors

Objective: This phase I trial was designed to determine the maximal tolerated dose (MTD) of the combination of topotecan and gemcitabine given in a weekly schedule. Materials and Methods: In this single-arm, open label, dose-escalation study, we administered topotecan (0.75-1.5 mg/m²) and gemcitabine (1000 mg/m²) on days 1, 8, and 15 every 4 weeks to 25 patients with advanced solid tumors. Results: The topotecan MTD, when combined with gemcitabine, was 1.25 mg/m²/wk. Dose-limiting toxicities consisted of febrile granulocytopenia in 2 patients at the highest dose level. At the MTD, no episodes of granulocytopenia were observed, whereas 2/9 patients exhibited grade 3 thrombocytopenia. Other common grades 3-4 adverse events across all cohorts included non-neutropenic infections, fatigue, skin reactions, vomiting, and fever. One partial response and 2 stable diseases were observed in patients with nasopharyngeal carcinoma. Disease stabilization was also observed in patients with squamous cell carcinoma of the head and neck (3), nonsmall cell lung cancer (1), and thymoma (1). Conclusions: Topotecan and gemcitabine combined in a weekly schedule exhibit a favorable toxicity profile. Efficacy results support the further evaluation of this regimen in patients with head and neck cancer (particularly nasopharyngeal carcinoma).