A phase I study of concurrent weekly topotecan and cisplatin chemotherapy with whole pelvic radiation therapy in locally advanced cervical cancer: a gynecologic oncology group study

To determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLT) of intravenous topotecan administered with weekly cisplatin during pelvic radiation therapy in patients with locally advanced cervical cancer. Patients were treated at one of two dose levels receiving intravenous topotecan at 0.5mg/m(2) and cisplatin at either 30 or 40 mg/m(2) given weekly for 6 weeks concurrently with pelvic radiation and intracavitary brachytherapy. The primary endpoint for the escalation study was acute dose-limiting toxicities occurring within 30 days of completing radiation therapy. Eleven patients were enrolled. Dose-limiting toxicity consisting of Grade 3 nausea and vomiting lasting >24h in one patient and grade 3 febrile neutropenia in another patient occurred at the first dose level of weekly topotecan 0.5mg/m(2) and cisplatin 40 mg/m(2). This necessitated de-escalation to weekly cisplatin 30 mg/m(2) in combination with topotecan 0.5mg/m(2) and pelvic radiation. This dose level was tolerable in 6 evaluable patients with only one DLT consisting of grade 4 thrombocytopenia, grade 3 abdominal pain and grade 3 elevated gamma glutamyl transpeptidase (GGT). In women with locally advanced cervical cancer, intravenous topotecan 0.5mg/m(2) and cisplatin 30 mg/m(2) given weekly for 6 weeks with concurrent pelvic radiation and intracavitary brachytherapy were tolerable. Further expansion of the feasibility cohort of this study was suspended based on the results of a phase 3 trial comparing the efficacy of platinum combinations in advanced and recurrent cervical cancer