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).
Highlights
Peritoneal metastasis (PM) is a common manifestation of gynecological carcinomas and has significantly negative influence on patient prognosis [1]
Twenty-seven (90%) patients had a pathological diagnosis of primary ovarian cancer, while 3 (10%) patients had PM from other sites
Before hyperthermic intraperitoneal chemotherapy (HIPEC), 9 (30%) patients received only biopsy because of unresectable disease, and they underwent two cycles of intravenous neoadjuvant chemotherapy followed by interval debulking surgery
Summary
Peritoneal metastasis (PM) is a common manifestation of gynecological carcinomas and has significantly negative influence on patient prognosis [1]. For PM patients, a combination of cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) is an important treatment option. Malignant cells can be killed by hyperthermia in the range of 41–43◦C [2]. Previous clinical studies have noted improved survival outcomes among PM patients. Dose of Hyperthermic Cisplatin treated with HIPEC [3,4,5]. On the basis of this evidence, many guidelines recommend HIPEC for gynecological cancer patients with PM [6,7,8]. To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43◦C among gynecological cancer patients
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