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). The most common hematologic toxicity was grade 3 lymphopenia (n=9). Only one patient experienced grade 3 neutropenia. Of 3 delayed weekly cycles, none were due to hematologic toxicity. Other main toxicities included: grade 3 leukopenia (n=6), grade 3 coagulation (n=1), grade 3 fatigue (n=2), grade 3 G.I. (n=3), lymphocysts (n=2), non-neutropenic fever (n=2). Six patients required blood transfusion during therapy. Only 3 patients required r-erythropoetin. Only one patient had persistent disease diagnosed within the six months following completion of treatment while the rest had complete responses. Conclusions: The administration of 0.15 mg/m2/day topotecan as a continuous infusion in conjunction with cisplatin and radiation is reasonably well tolerated and appears clinically active in advanced cervical cancer. Thromboembolic complications, frequent in cervical cancer patients, may lead to alternative delivery methods in future clinical trials. No significant financial relationships to disclose.