High-intensity intravenous cyclophosphamide and cisplatin, interim surgical debulking, and intraperitoneal cisplatin in advanced ovarian carcinoma: a pilot trial with ten-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 METHODS

Forty patients with stage IIB through IV ovarian cancer were entered and 36 were evaluable for response and survival and approximately 10 years. Following a first laparotomy for diagnosis and debulking, the patients received two cycles, spaced 28 days apart, of intravenous cisplatin 30-40 mg/m2/day with hypertonic saline for 4 to 5 days and cyclophosphamide 200 mg/m2/day for 5 days. A second laparotomy was done to further debulk remaining cancer and to place an intraperitoneal catheter. Four cycles of intraperitoneal cisplatin at 50 or 100 mg/m2 were administered 21 days apart and followed by a third laparotomy to define response and plan any further therapy.

RESULTS

The surgically confirmed complete response rate was 47% and median survival is 68.3 months for this group. Ten of the 17 patients (58.8%) relapsed following complete response at a median of 19.5 months (range, 5-98). Both aggressive chemotherapy and surgery seemed to play a role in inducing this high complete response rate. Traditional prognostic factors, including stage and diameter of largest residual disease, had little apparent 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 limiting.

CONCLUSION

In the context of recent data failing to support any clinical benefit to modest increases in dose escalations of cisplatin or carboplatin, in this trial the high complete response rate suggests that the multimodality approach (i.e., interval surgical debulking and intraperitoneal cisplatin) is worthy of further study. The high relapse rate among complete responders and the unacceptable neurotoxicity also suggest that modifications could improve the results. The use of newer agents and further intensification (substituting carboplatin for cisplatin and the use of paclitaxel) with stem cell support are two examples.