Phase I study of topotecan continuous infusion and weekly cisplatin with radiation therapy for locally advanced/recurrent cervical cancer

5129 Background: Topotecan is a topoisomerase -1 inhibitor with radiosensitizing effects. The combination of topotecan with cisplatin has shown clinical activity against cervical cancer. Methods: Patients with stages IB2- IVA or recurrent cervical cancer who had not received prior radiation or chemotherapy were eligible. Topotecan was administered as a continuous I.V. infusion for 5 days each week through a central venous catheter. Dose levels evaluated were 0.05 (n= 7), 0.1 (n=7) and 0.15 (n= 5) mg/m2 / day. Cisplatin was administered I.V. weekly at 20 mg/m2. Conventional doses of pelvic and para-aortic radiation were administered. Results: Ninety seven, 92 and 96% of all cycles for each dose level were administered on schedule. Onlythree patients did not complete the full treatment course: one due to noncompliance and two due to grade 4 thromboembolic complications (one patient in dose level 1 with a septic superior vena cava thrombus leading to death and another in dose level 3 with a pulmonary embolus...