A phase I study of docetaxel as a radiosensitizer for locally advanced squamous cell cervical cancer

Abstract

5053 Background: Concomitant radiotherapy with cisplatin chemotherapy is the standard of care for locally advanced squamous cell cervical cancer (LASCCC). Alternatives to cisplatin are needed due to patient intolerance or toxicity. Taxanes have demonstrated clinical cytotoxic activity to SCCC and in-vitro radio-sensitization. This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy for the primary treatment of LASCCC. Methods: Twenty-three patients with FIGO stage IIB-IVA LASCCC without para-aortic lymph node involvement were screened and 13 enrolled in a dose-escalating phase I study. Docetaxel dose levels were 20 mg/m2, 30 mg/m2 and 40 mg/m2 given intravenously every 7 days for 6 cycles. Three patients were treated at each dose level and six patients received the MTD. Radiation therapy (RT) delivered a total dose of approximately 85 Gy to Point “A”. RT was administered with megavoltage external beam irradiation (EBI) at 1.8 Gy/fraction (fx) for 30 fxs to the pelvis over 6 weeks using a 4-field “box” technique for the first 25 fxs. A midline shield was applied for the last 5 fxs. Following EBI, patients underwent low-dose-rate brachytherapy. Results: Thirteen patients completed 4 - 6 cycles of chemotherapy. The other patients withdrew consent or needed alternative treatment before initiating the study. Reasons for completing less than 6 cycles were: noncompliance (5), adverse event (2), progression (1). One patient was lost to follow-up after 4 cycles. DLT’s were not observed at the 20 mg/m2 dose level. At the 30 mg/m2 dose level, 1/4 patient had a treatment-unrelated pelvic abscess and celiotomy. Another had progression 4 months after treatment. At the 40 mg/m2 dose level, 1/6 patients had progression and experienced grade 2 pneumonia, not treatment related. DLT was not observed in 6 patients at the 40 mg/m2 level. Overall, 5/13 (38%) experienced grade 2 diarrhea, 5 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. Seven of 9 patients (78%) had no evidence of disease with follow-up ranging from 10–21 months. Conclusions: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for LASCCC is 40 mg/m2. The phase II trial is underway. No significant financial relationships to disclose.