A phase I / II study of concurrent cisplatin chemotherapy in patients with carcinoma of the cervix receiving pelvic radiotherapy

Abstract

Objective To define the maximum tolerated dose (MTD) of weekly cisplatin in concurrent chemoradiotherapy for Chinese cervical carcinoma.Methods Cervical carcinoma of stage ⅠB2- ⅣA were eligible for the study.Phase Ⅰ study was dose-escalation trial with 15 patients.All patients received whole pelvic radiotherapy with three dimentional conformal radiotherapy technique. Concurrent cisplatin started from the dose of 20 mg/m2 to 25 mg/m2,30 mg/m2,35 mg/m2,40 mg/m2 for the weekly schedule ( ≥3 patients per dose group) and the doses were steadily escalated to 40 mg/.m2.If the dose was increased to 40 mg/m2 without dose-limiting toxicity ( DLT),40 mg/m2 would be the maximum tolerated dose (MTD).According to the MTD dose from Phase Ⅰ study,we conducted phase Ⅱ clinical trial with 36 patients.Results In Phase Ⅰ study,cisplatin dose was escalated to 40 mg/m2 and DLT had not been reached.Thirty-six patients in Phase Ⅱ study included 9 inpatients and 27 outpatients.All 9 inpatients completed 6 cycles of chemotherapy. In 27 outpatients,18 patients (66％) completed 6 cycles of chemotherapy,19 patients (70％) completed 5 cycles and 25 patients (92％) completed 4 cycles of chemotherapy.All patients completed radiotherapy.Major adverse effects were grade 1 and 2 gastrointestinal toxicities and neutropenia.Conclusions Weekly 40 mg/m2 cisplatin concurrent with radiotherapy is well tolerated when given to Chinese patients with cervical carcinoma. For outpatients with poor performance status,the cisplatin dose needs to be reduced. Key words: Cisplatin; Maximum tolerated dose; Cervical neoplasms/concurrent radiochenmotherapy; Toxicity