Ovarian cancer stage

NASHVILLE, TENN. -- Women with newly diagnosed ovarian cancer may be eligible for gene therapy to treat their disease, according to a pioneer in the field.

Until now, only ovarian cancer patients who had failed multiple conventional treatments of chemotherapy or radiation were eligible to participate in clinical trials of gene therapy. But recruitment of newly diagnosed patients is now underway for a phase III trial of this treatment, Dr. Richard Buller said at the annual meeting of the Society of Gynecologic Oncologists.

The trial is designed to compare first-line p53 gene therapy in combination with chemotherapy versus first-line chemotherapy alone in newly diagnosed patients.

"This study is designed to detect a 40% improvement in survival rates [over conventional treatments], so there's a degree of confidence that this could be a home run. ... It's not likely to cure the disease for everybody, but it may be a quantum leap forward," Dr. Buller, director and professor of gynecologic oncology at the University of Iowa, Iowa City, said in an interview.

Currently there are a number of ongoing trials to assess different gene therapy strategies for ovarian cancer, he said.

Dr. Buller described his experience using p53 gene transfer in patients who have failed multiple previous conventional treatments. "In a heavily pretreated group you'd expect them all to be dead long ago, but for our 24 patients who received multiple gene transfer treatments, 12 of them lived more than 20 months and 3 are still alive more than 3 years after they entered the study," he said at the meeting.

The 13-month median survival rate of his study patients compares favorably with the 16-month median survival rate in patients treated with second-line chemotherapy. "It's almost as effective as Taxol as a second-line treatment, yet these are patients for whom this is a fourth- or fifth- or even sixth-line treatment," he said.

Patients must be diagnosed with stage III disease and have undergone surgery and an initial cycle of platinum-based chemotherapy, with less than 2 cm of residual disease after surgery. In addition, a biopsy of their tumor must confirm a mutation of the p53 gene.

"About 75% of patients with advanced ovarian cancer have a p53 gene mutation, but it's not a routine test, so their physician would have to send us a sample of paraffin-embedded tissue from their pathology lab," Dr. Buller noted. So far, 130 of the planned 360 patients have received a single cycle of chemotherapy and have been randomized to receive five more cycles of chemotherapy alone or chemotherapy plus intraperitoneal gene replacement. The study is sponsored by Schering-Plough Corp.