Topotecan Concomitant with Primary Brachytherapy Radiation in Patients with Cervical Carcinoma: A Phase I Trial

Objective. The aim of this study was to assess the toxicity of concomitant topotecan and radiation therapy in a Phase I study. Primary treatment for cervical carcinoma usually consists of surgery or radiation, with chemotherapy used in a neoadjuvant or concomitant fashion. There are in vitro data to suggest that topotecan is a radiosensitizing agent. Methods. Six patients with cervical cancer were recruited to this study. All patients had completed whole pelvic radiation therapy and were scheduled for low-dose brachytherapy. The patients were administered topotecan IV during their low-dose brachytherapy. The initial dose of topotecan was 0.5 mg/m2/day for 5 days concomitant with low-dose brachytherapy for two brachytherapy applications. Results. Three patients were accrued to the initial dose level. No major toxicity was noted at this dose level. Three patients were treated at the 1.0 mg/m2/day dose level; however, significant toxicity was noted at this level. (Two patients experienced grade 4 and one a grade 3 hematologic toxicity). Conclusion. Significant marrow toxicity was noted with concomitant topotecan and intracavitary radiation at 1.0 mg/m2/day. The maximum tolerated dose in this trial was 0.5 mg/m2/day for 5 days of topotecan concomitant with low-dose brachytherapy.