A phase I study of gemcitabine followed by cisplatin concurrent with whole pelvic radiation therapy in locally advanced cervical cancer: a Gynecologic Oncology Group study.

PURPOSE: To determine the maximum tolerated dose (MTD) of gemcitabine followed by cisplatin that can be administered weekly during pelvic radiation therapy in patients with locally advanced cervical cancer.
METHODS: A phase I and feasibility study with dose escalation of gemcitabine in cohorts of three to six patients to determine the MTD (the dose level at which no more than one of six patients experienced a acute dose-limiting toxicity) was conducted.
RESULTS: Thirteen patients were entered on the phase I trial. Acute dose-limiting toxicity occurred with weekly cisplatin at a dose of 40 mg/m(2) and gemcitabine at a dose of 100 mg/m(2). The study was modified, decreasing the dose of cisplatin to 30 mg/m(2) in an effort to dose escalate gemcitabine. Acute dose-limiting toxicity occurred again with weekly cisplatin at a dose of 30 mg/m(2) and gemcitabine at a dose of 75 mg/m(2) (dose level 3). In addition to acute hematologic and acute and late non-hematologic toxicities, late grade 3 and 4 GI and GU toxicities have occurred in two of six patients at dose level 3. Twelve of thirteen patients remained disease-free following treatment.
CONCLUSION: The MTD found in this chemoradiation study was weekly gemcitabine 50 mg/m(2) followed by cisplatin 40 mg/m(2). The alternative drug sequence has been reported by others to allow higher doses of gemcitabine. However, at this dose level chronic toxicity was observed. Further expansion of the feasibility cohort of this study was suspended pending the efficacy and toxicity results of a large trial which has recently been completed.