KEY TAKEAWAYS
- The phase I trial aimed to determine the MTD of paclitaxel + cisplatin delivered as HIPEC in OC patients.
- The results demonstrated that in OC patients post-debulking surgery, HIPEC with paclitaxel and fixed cisplatin was safely administered.
Paclitaxel serves as a complement to cisplatin in hyperthermic intraperitoneal chemotherapy (HIPEC). Jing Li and his research group spearheaded the study that aimed to determine the maximum tolerated dose (MTD) of paclitaxel in combination with a fixed cisplatin dose (75 mg/m2) delivered through HIPEC for ovarian cancer (OC) patients.
The study utilized a Bayesian Optimal Interval (BOIN) design with a target dose-limiting toxicity (DLT) rate of 25% and a maximum sample size of 30 patients. To expedite the trial, initial dose escalation employed a cohort size of one, transitioning to a cohort size of three after the first observed DLT. Paclitaxel started at 175 mg/m2 with subsequent dose decisions made by a Data and Safety Monitoring Board in 25 mg/m2increments. The process continued until reaching the maximum sample size or treating 12 patients at a given dose.
Of 21 trial patients, no DLTs occurred in the 150 mg/m2 paclitaxel group (3 evaluable patients). In the 175 mg/m2 group (12 evaluable patients), two patients experienced DLTs, including one case of grade 4 neutropenia and one case of grade 4 anemia, neutropenia, and leucopenia. In the 200 mg/m2 paclitaxel group (6 evaluable patients), 4 patients experienced DLTs, including one case of grade 4 constipation, one case of grade 3 kidney injury, and two cases of grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% CI, 0.02-0.42), closest to the targeted DLT rate, and thus selected as the MTD.
The results demonstrated that in OC patients undergoing debulking surgery followed by HIPEC at 43°C for 90 minutes, the combination of paclitaxel and a fixed dose of cisplatin (75 mg/m2 was safely administered intraperitoneally at a dose of 175 mg/m2 The study was sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/28
Clinical Trial: https://clinicaltrials.gov/study/NCT05620654
Wu M, Lin Z, Lai Y, et al. ‘’ Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.’’ Presented at ESMO ASIA Congress 2023.’’(Presentation Number 291MO)
