Intraoperative intraperitoneal (IP) chemotherapy with cisplatin and escalated dose of epinephrine in patient with recurrent peritoneal carcinomatosis of ovarian cancer: A phase I study

Abstract

16019 Background: IP epinephrine (E) has been shown to enhance the accumulation and antitumor activity of IP cisplatin in rats with peritoneal carcinomatosis (Duvillard et al. Int J Cancer, 1999). E induces a vasoconstriction of peritoneal vascular bed which limits platin peritoneal leakage and enhances drug penetration into tumor nodules. Results of a phase I study with the association of IP E and IP cisplatin in patient with refractory peritoneal carcinomatosis has been reported (Molucon-Chabrot et al, Anticancer Drugs, 2006). We conducted a phase I study to evaluate intraoperative IP chemotherapy with the association of cisplatin and escalated dose of E. Methods: 18 patients (pts) with recurrent ovarian cancer were enrolled. The median age was 56 years old (range 42–66). After an optimal cytoreductive surgery, IP chemotherapy was performed during surgery by filling twice the peritoneal cavity with 3 liters of an isotonic saline pre heated at 37°C and 90 mg of cisplatin associated with increasing concentrations of E during 1 hour. Results: E was escalated according to the following dosage: 0, 1, 2, 3 mg/L (3 pts by step). No toxicity was observed during and after intraoperative IP chemotherapy in the first 10 patients. The 2nd patient included in the 3 mg/L level of E experienced a tachycardia ≥ 120/min, ventricular extrasystoles (VES) ≥ 2/min, increase of troponine plasmatic concentration without significant electric sign of cardiac ischemia. The 3rd patient at this level experienced a tachycardia ≥ 120/min with ventricular VES ≥ 2/min and no increase of troponine concentration or electric sign of cardiac ischemia. According to the protocol design, 6 additional patients were included in the lower dose of 2 mg/L of E and no toxicity occurred. One can consider that the recommended dose of E was established. Conclusion: The combination of IP E with IP cisplatin in intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The limiting toxicity was the cardiovascular effect which occurred with 3 mg/L dose of E. A phase II-III study is planned to investigate if IP chemotherapy adds to a second look surgery for the initial treatment of stage III ovarian carcinoma. No significant financial relationships to disclose.