HIGH-INTENSITY INTRAVENOUS CYCLOPHOSPHAMIDE AND CISPLATIN, INTERIM SURGICAL DEBULKING, AND INTRAPERITONEAL CISPLATIN IN ADVANCED OVARIAN-CARCINOMA - A PILOT TRIAL WITH 10-YEAR FOLLOW-UP

Purpose. This trial was undertaken to study the effect of intensified intravenous cyclophosphamide/cisplatin and interim surgical debulking, followed by intraperitoneal cisplatin on surgically defined complete remission rate and survival in advanced ovarian cancer. Patients and m ethods. Forty patients with stage IIB through IV ovarian cancer were e ntered and 36 were evaluable for response and survival for approximate ly 10 years. Following a first laparotomy for diagnosis and debulking, the patients received two cycles, spaced 28 days apart, of intravenou s cisplatin 30-40 mg/m(2)/day with hypertonic saline for 4 to 5 days a nd cyclophosphamide 200 mg/m(2)/day for 5 days. A second laparotomy wa s done to further debulk remaining cancer and to place an intraperiton eal catheter. Four cycles of intraperitoneal cisplatin at 50 or 100 mg /m(2) were administered 21 days apart and followed by a third laparoto my to define response and plan any further therapy. Results. The surgi cally confirmed complete response rate was 47% and median survival is 68.3 months for this group. Ten of the 17 patients (58.8%) relapsed fo llowing complete response at a median of 19.5 months (range, 5-98). Bo th aggressive chemotherapy and surgery seemed to play a role in induci ng this high complete response rate. Traditional prognostic factors, i ncluding stage and diameter of largest residual disease, had little ap parent effect on Likelihood of complete response or survival, whereas tumor grade had a more significant effect on survival. Nadir fever was experienced by 33% of patients but peripheral neuropathy was dose lim iting. Conclusion. in the context of recent data failing to support an y clinical benefit to modest increases in dose escalations of cisplati n or carboplatin, in this trial the high complete response rate sugges ts that the multimodality approach (i.e., interval surgical debulking and intraperitoneal cisplatin) is worthy of further study. The high re lapse rate among complete responders and the unacceptable neurotoxicit y also suggest that modifications could improve the results. The use o f newer agents and further intensification (substituting carboplatin f or cisplatin and the use of paclitaxel) with stem cell support are two examples. (C) 1997 Academic Press.