Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Clinical research design division, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
J Gynecol Oncol. 2024 Jan;35(1):e1. doi: 10.3802/jgo.2024.35.e1. Epub 2023 Jul 5.
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.
In this phase I trial, a time-to-event Bayesian optimal interval design was used. Docetaxel was given at a starting dose of 60 mg/m² and was increased in 5 mg/m² increments until the MTD was determined or the maximum dose level of 75 mg/m² was reached. The dose-limiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes.
From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m², no DLT was reported. DLTs were observed in one patient who received 70 mg/m² docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m² docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD.
Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m²), can be used safely at intraperitoneal doses of 75 mg/m² in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.
ClinicalTrials.gov Identifier: NCT05410483.
确定多西他赛联合固定剂量顺铂（75mg/m²）作为腹腔热灌注化疗（HIPEC）在卵巢癌患者中的最大耐受剂量（MTD）。
在这项 I 期试验中，采用了时间事件贝叶斯最优区间设计。多西他赛起始剂量为 60mg/m²，每 5mg/m²递增，直到确定 MTD 或达到 75mg/m²的最大剂量水平。剂量限制性毒性（DLT）率设定为 25%，总样本量为 30 例。HIPEC 在减瘤手术后立即进行，目标温度为 43°C，持续 90 分钟。
2022 年 8 月至 2022 年 11 月，共纳入 30 例患者。在接受≤65mg/m²多西他赛剂量的患者中，未报告 DLT。70mg/m²多西他赛组 1 例患者（3 级贫血）和 75mg/m²多西他赛组 3 例患者（1 例 3 级贫血、1 例 3 级肝损伤和 1 例 4 级血小板减少）出现 DLT。接受 75mg/m²多西他赛联合 75mg/m²顺铂治疗的患者，估计 DLT 率为 25%，最接近目标 DLT 率，因此被选为 MTD。
在接受减瘤手术后，多西他赛联合固定剂量顺铂（75mg/m²）可安全地以 75mg/m²的腹腔剂量用于卵巢癌患者的 HIPEC（43°C，90 分钟）。
ClinicalTrials.gov 标识符：NCT05410483。
