INTRAPERITONEAL CISPLATIN AND REGIONAL HYPERTHERMIA FOR OVARIAN-CARCINOMA

Purpose: To review the theoretical basis and results of a Phase I stud y of concurrent intraperitoneal cisplatin and hyperthermia in the trea tment of ovarian carcinoma. Methods and Materials: Previously treated patients with epithelial ovarian carcinoma received intraperitoneal in stillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5-degrees-C. Cisplatin dose started at 20 mg/ m2 with escalation to the maximally tolerated dose. Six such cycles gi ven every 3 weeks were planned. Pharmacokinetic studies with and witho ut hyperthermia were performed. Results: Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temp erature was 40.7-degrees-C; the majority of treatments in which the go al temperature was not reached had power limited by patient discomfort . No major toxicities attributable to hyperthermia were noted. Pharmac okinetic studies noted no significant differences between treatments w ith vs. without hyperthermia, with intraperitoneal to plasma area unde r the curve ratios being 30-35. Ten patients had a decline in their CA -125 count during treatment, although in only two patients did this re sponse persist beyond their course of treatment. Conclusion: Intraperi toneal cisplatin and regional hyperthermia can be performed with reaso nable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretre ated patients (which is similar to those reported with cisplatin alone ) and median intraperitoneal temperatures of 40.7-degrees-C, however, are felt to be too low to be efficacious in a significant percentage o f women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.