AUTHOR=Chan Chui-ying , Li Hui , Wu Miao-fang , Liu Chang-hao , Lu Huai-wu , Lin Zhong-qiu , Li Jing
TITLE=A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy
JOURNAL=Frontiers in Oncology
VOLUME=11
YEAR=2021
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.616264
DOI=10.3389/fonc.2021.616264
ISSN=2234-943X
ABSTRACT=Background: To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C among gynecological cancer patients.
Methods: 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/m2, 75 mg/m2, 80 mg/m2 and 85 mg/m2), and 30 patients.
Results: 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/m2) and included acute kidney injury, pulmonary embolism, anemia, and neutropenia. When cisplatin was given at dose level four (85 mg/m2), the isotonic estimate of the DLT rate (22%) was closest to the target DLT rate of 20%. Therefore, 85 mg/m2 was selected as the MTD, with a 51% probability that the toxicity probability was greater than the target DLT rate.
Conclusions: For gynecological cancer patients who received HIPEC for peritoneal metastases, the MTD of cisplatin in HIPEC at 43°C was 85 mg/m2. Our findings apply to patients who do not receive bevacizumab (ChiCTR1900021555).