Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: Twenty-four-hour versus 7-day infusion

Purpose: To compare the toxicity, pharmacokinetics, an efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (IF) interleukin-2 (IL-2) by two different infusion schedules. Patients and Methods: Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m(2)/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy, Eligibility criteria included greater than or equal to six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer. Results: Forty-one eligible patients received IP IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m(2) as the maximum-tolerated dose (MID), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established, Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35), The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%, For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months). Conclusion: IP IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to IP IL-2 therapy or other factors that cannot be controlled for in a single-arm study. (C) 1997 by American Society of Clinical Oncology.