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

Zhi-Yao You, Miao-Fang Wu, Hui Li, Yan-Fang Ye, Li-Juan Wang, Zhong-Qiu Lin, Jing Li, Zhi-Yao You, Miao-Fang Wu, Hui Li, Yan-Fang Ye, Li-Juan Wang, Zhong-Qiu Lin, Jing Li

Abstract

Objective: 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 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT05410483.

Keywords: Cisplatin; Docetaxel; Hyperthermic Intraperitoneal Chemotherapy; Maximum Tolerated Dose; Ovarian Cancer.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Figures

Fig. 1. Time-to-event Bayesian Optimal Interval Design.…
Fig. 1. Time-to-event Bayesian Optimal Interval Design. According to the time-to-event Bayesian optimal interval (TITE-BOIN) design, the decision to escalate or de-escalate the dose was made by a comparison of the observed DLT rate at the current dose with fixed prespecified dose escalation and de-escalation boundaries. We sought to determine the MTD for hyperthermic docetaxel with a target DLT rate of 25%, 4 prespecified doses (60 mg/m2, 65 mg/m2, 70 mg/m2 and 75 mg/m2) and 30 patients. The corresponding dose escalation and de-escalation boundaries were 0.197 and 0.298, respectively.
DLT, dose-limiting toxicity; MTD, maximum tolerated dose.
Fig. 2. Patient-reported outcomes. (A) Symptom burden.…
Fig. 2. Patient-reported outcomes. (A) Symptom burden. (B) Symptom interference over time.
ID, identification.

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