Objective: The toxicity and activity of intravenous topotecan were assessed in a multicenter Phase II study (GOG 76-U) in patients with advanced, recurrent, or persistent squamous cell carcinoma of the uterine cervix.
Methods: Intravenous topotecan was administered at 1.5 mg/m2 per day for 5 consecutive days every 4 weeks in patients without prior chemotherapy, aside from chemosensitizing agents used in conjunction with radiotherapy. The study required histologic confirmation of primary diagnosis, adequate performance status, and measurable disease to assess response. A two-stage design for accrual was used to allow for early termination of the study should inadequate response or excessive toxicity be an issue. Modifications of dose were based on hematologic toxicity. Treatment was continued until progression of disease was documented or adverse effects prohibited further therapy.
Results: A total of 49 patients were entered on study: of these 5 were never treated, and 1 was not evaluable for response. More than 88% (38 of 43 patients) had received prior radiotherapy. A median of two courses were administered per patient with a range of 1 to 14 cycles. Grade 4 neutropenia occurred in 68% and grade 4 thrombocytopenia in 18% of patients. Nonhematologic toxic effects were infrequent and not dose-limiting. The overall response rate (complete and partial) was 18.6%. The median progression-free survival was 2.4 months.
Conclusions: Topotecan administered at this dose and schedule demonstrated moderate activity albeit at a cost of substantial hematologic toxicity in patients with advanced, recurrent, or persistent squamous cell carcinoma of the cervix.