IP Interleukin-2 Shows Durable Responses in Ovarian Cancer

ASCO LOS ANGELES--A review of survival data from a phase I studyof intraperitoneal interleukin-2 (IL-2) performed from 1987 to1990 has shown durable responses in women with refractory ovariancancer.

Speaking at a media briefing held in conjunction with the AmericanSociety of Clinical Oncology meeting, Robert P. Edwards, MD, saidthat the study was "ahead of its time." RecombinantIL-2 (aldesleukin, Proleukin) had become available in 1985, andgiving it to ovarian cancer patients in the IP cavity as locoregionaltreatment "was really an insightful thing to do," headded.

A phase II study of the treatment is planned at the Universityof Pittsburgh/Magee-Womens Hospital, where Dr.Edwards is director,Division of Gynecologic Oncology, and if the promising phase Iresults are confirmed, intraperitoneal IL-2 could offer an effectivesecond-line therapy for patients with recurrent ovarian cancer.

The original University of Pittsburgh investigators, Drs. Herbermanand Kirkwood, used escalating doses of two different deliveryschedules: 7-day continuous infusion every other week or a weekly24-hour infusion.

The investigator's initial bias, based on animal data, was thatthe 7-day infusion would be superior. "However," Dr.Edwards said, "it became clear around 1990 that toxicitywith the 7-day infusion was excessive, and the weekly infusionproduced more responses, although this did not reach significance."

Dr. Edwards and his colleagues determined long-term survivorsfrom the study by reviewing the patients' charts and contactingsurvivors. They found that the patients who responded at the lowerdose tiers were still alive and free of disease 57 to 84 monthsafter treatment.

"These are patients who had persistent ovarian cancer afterreceiving very intensive chemotherapy," Dr. Edwards stressed.The majority had received three- drug regimens that included platinumand doxorubicin. All underwent surgical evaluation to documentthe extent of disease prior to treatment with IL-2.

Median Survival Not Yet Reached

Of 41 patients treated on this protocol, 35 were considered evaluable,and of those 35, nine responded to intraperitoneal IL-2 (six completeresponses and three partial responses). Six were still alive asof May, 1995, and five were free of disease. Median survival forthe responders has not yet been reached. "It has gone beyond60 months," he said.

Dr. Edwards finds it particularly exciting that patients who achieveda reduction in disease volume to optimal residual disease hada 33% response rate. Four of the six responders from that groupare still alive.

He also pointed out that most of the patients who responded hadhigh-grade disease, which he found very encouraging since recurrenceof high-grade disease is "essentially an incurable situation."

Four of five patients who had microscopic disease responded tointraperitoneal IL-2, as determined by laparotomy and follow-upbiopsies. Of those four responders, "every single patientis alive and free of disease between 57 and 84 months," hesaid.

Although the numbers are small and the intention of the originalstudy was to define toxicity, not activity, "we are veryexcited about this regimen," he said.

For More Information

For information about gynecologic cancer treatments using IL-2,please call Magee-Womens Hospital's Oncology Outreach Serviceat 1-800-641-1662 or the University of Pittsburgh Cancer Instituteat 1-800-237-4724.