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

Purpose: 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. Methods: Patients were treated at one of two dose levels receiving intravenous topotecan at 0.5 mg/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. Results: Eleven patients were enrolled. Dose-limiting toxicity consisting of Grade 3 nausea and vomiting lasting > 24 h in one patient and grade 3 febrile neutropenia in another patient occurred at the first dose level of weekly topotecan 0.5 mg/m ² and cisplatin 40 mg/m ². This necessitated de-escalation to weekly cisplatin 30 mg/m ² in combination with topotecan 0.5 mg/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). Conclusions: In women with locally advanced cervical cancer, intravenous topotecan 0.5 mg/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.