Taxane-refractory PCa: Regimens offer modest results

September 1, 2006

Atlanta-A trial of drug regimens in hormone-refractory prostate cancer came up with only modest results, but it did take an important first step: It is one of the first prospective trials conducted in taxane-refractory disease.

Atlanta-A trial of drug regimens in hormone-refractory prostate cancer came up with only modest results, but it did take an important first step: It is one of the first prospective trials conducted in taxane-refractory disease.

In the study, 82 men with metastatic progressive disease with an Eastern Cooperative Oncology Group performance status of zero to two were randomly assigned to either ixabepilone, 35 mg/m2 IV every 3 weeks, or mitoxantrone, 14 mg/m2 every 3 weeks and prednisone, 5 mg twice a day. The median number of cycles for each treatment was three. Then, based on progression or toxicity, patients were allowed to cross over to the other treatment. The primary endpoint was a confirmed PSA decline of 50% or more.

"Although some patients went for 12 cycles, or about 9 months, most progressed very rapidly," noted principal investigator Jonathan Rosenberg, MD, assistant clinical professor of medicine at the University of California, San Francisco Comprehensive Cancer Center.

For third-line therapy, the response rate was 12% for ixabepilone, 31% for mitoxantrone/prednisone, and one RECIST partial response in each (with overlapping confidence intervals).

Where to go next

The study wasn't designed to compare the treatments per se, but the treatments were roughly equivalent, and there was not a substantial amount of activity by PSA response.

"Mitoxantrone looks more active than we expected," Dr. Rosenberg told Urology Times. "We thought, based on the laboratory data, that ixabepilone would be highly active in this taxane-resistant prostate cancer population because it was active in taxane-resistant cell lines and in animal models, but there was not a substantial amount of activity by PSA response."

Although results were somewhat disappointing, one important finding of this study is that the survival in these patients after taxanes have failed is about 12 to 13 months, "and it's a good baseline for where we go next in terms of clinical trial design," Dr. Rosenberg said.

"We really need to be putting patients on clinical trials in this population to establish what is the next therapy in taxane-resistant patients," he said. "And if we come up with something very good, we hope we'll be able to test it against docetaxel and define a new standard if it really is better. The goal isn't to just get better second-line therapies, but to use the second line as a platform to test better therapies in the first-line setting eventually."

Session leader Nancy Dawson, MD, of the University of Maryland Medical Center in Baltimore, echoed this sentiment.

"Second- and third-line treatment for hormone-resistant prostate cancer is a true unmet need of our patients," Dr. Dawson said.

She and Dr. Rosenberg hope urologists and oncologists will help fill that tremendous need.

Currently, for this patient population, there is one randomized, phase III study of satraplatin, an oral platinum analog, "and we may hear data in the next months to a year or so," said Dr. Rosenberg.

This study was sponsored by the Cancer Treatment and Evaluation Program of the National Cancer Institute, and financially supported by Bristol-Myers Squibb. Some of the co-investigators have served as consultants for Bristol-Myers