HIPEC ROC I: A phase 1 study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postop IV platinum-based chemo in pts with platinum-sensitive recurrent OC

abstract

This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels—60, 80 and 100 mg/m². After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41–43°C.

Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m². The remaining five patients treated with 100 mg/m² tolerated their treatment well. The recommended phase II dose was established at 100 mg/m². The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples.

Common postoperative grade 1–3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m² has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m². The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.