A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer.

Abstract

e17532 Background: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this single-center Phase I trial, time-to-event Bayesian Optimal Interval Design (TITE-BOIN) was used. The starting dose for docetaxel was 60 mg/m2, with escalation in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The target dose-limiting toxicity (DLT) rate was 25%, and the total sample size was 30 patients. HIPEC was delivered immediately following the debulking surgery using the closed technique with a target temperature of 43 ℃ for 90 minutes. Results: A total of 30 patients were enrolled from August 2022 to November 2022. Among patients who received a docetaxel dose level ≤ 65 mg/m2, no DLT was reported. DLTs were observed in one patient at 70mg/m2 docetaxel (grade 3 anemia) and three patients at 75mg/m2 docetaxel (one grade 3 anemia, one grade 3 hepatic impairment and one grade 4 thrombocytopenia). When patients were treated with docetaxel at a dose of 75 mg/m2 in combination with 75 mg/m2 cisplatin, the estimated DLT rate was 25% which was closest to the target DLT rate and therefore selected as the MTD. Conclusions: For ovarian cancer patients who receive HIPEC following debulking surgery, docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be safely used at intraperitoneal doses of 75 mg/m2(ClinicalTrials.gov identifier, NCT05410483).