A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy.

To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C among gynecological cancer patients. In this Phase I dose-finding trial, Bayesian optimal interval (BOIN) design was used. We sought to explore the MTD with a target dose-limiting toxicity (DLT) rate of 20%, 4 prespecified doses (70 mg/m, 75 mg/m, 80 mg/m and 85 mg/m), and 30 patients. Between 2019 and 2020, 30 gynecologic cancer patients were enrolled. No patients received bevacizumab in subsequent treatment. The most common adverse events related to cisplatin were nausea and vomiting (100%), followed by tinnitus (26.7%) and kidney injury (23.3%). Of the seven patients with kidney injury, four had persistent renal impairment, and finally progressed into chronic kidney injury. DLTs were noted only in the dose level 4 group (85 mg/m) and included acute kidney injury, pulmonary embolism, anemia, and neutropenia. When cisplatin was given at dose level four (85 mg/m), the isotonic estimate of the DLT rate (22%) was closest to the target DLT rate of 20%. Therefore, 85 mg/m was selected as the MTD, with a 51% probability that the toxicity probability was greater than the target DLT rate. For gynecological cancer patients who received HIPEC for peritoneal metastases, the MTD of cisplatin in HIPEC at 43°C was 85 mg/m. Our findings apply to patients who do not receive bevacizumab (ChiCTR1900021555).