Solo, combo chemo trials test new prostate cancer strategies

April 1, 2006

Beaver Creek, CO--For patients with hormone-refractory prostate cancer, the new standard of care is docetaxel (Taxotere)-based chemotherapy. The landmark TAX 327 study demonstrated an improvement in median survival and pain relief in patients with advanced, hormone-refractory disease who received this treatment regimen (N Engl J Med 2004; 351:1502-20). The challenge now is to look for new drug combinations that can provide additional benefits.

"There are quite a few clinical trials that combine docetaxel with other drugs to see if that drug can improve upon the benefits of the docetaxel alone," Philip Kantoff, MD, professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute, Boston, told Urology Times at the International Prostate Cancer Update here.

Randomized phase II, III trials

Dr. Kantoff called attention to randomized phase II and III trials that are either completed or are in process. Among the phase II trials is a completed randomized, double-blind study that showed no benefit with the addition of imatinib mesylate (Gleevec) to docetaxel. The results of this trial will be presented at the 2006 American Society of Clinical Oncology annual meeting in Atlanta.

A 240-patient study, now completed, produced evidence of a survival benefit with the addition of high-dose calcitriol to docetaxel in men with androdgen-independent prostate cancer (2005 ASCO annual meeting, abstract 4516). Another study of docetaxel with thalidomide (Thalomid) demonstrated an improvement in time to progression.

Two randomized phase III clinical trials currently are enrolling patients. The first is a study of patients with metastatic androgen-independent prostate cancer who will receive docetaxel with or without calcitriol. The second is a study of patients with prostate cancer who did not respond to hormone therapy who will receive docetaxel with or without bevacizumab.

"There are clinical trials in people who have failed docetaxel," Dr. Kantoff said, pointing to two completed trials of combination therapies for advanced prostate cancer.

One was a randomized phase III study of prednisone with or without satraplatin (still investigational) with progression-free survival as the primary endpoint. Currently, the data are being analyzed. The other compared ixabepilone (still investigational) and mitoxantrone (Novantrone).

Dr. Kantoff also discussed a series of clinical trials that evaluate the use of chemotherapy in early prostate cancer (see above, "Early disease targeted with chemotherapy").

"With all these ongoing trials using docetaxel, every patient with metastatic prostate cancer should enroll in one of these trials," said Nicholas J. Vogelzang, MD, director of the Nevada Cancer Institute, Las Vegas, and professor of medicine at the University of Nevada School of Medicine, Reno. "We need the support of the urologic community to move this field forward and to get some answers."

For a complete list of ongoing clinical trials for prostate cancer, visit http://www.clinicaltrials.gov/.

Dr. Kantoff has received funding from Amgen, Bayer, Bristol-Myers-Squibb, Genentech, and Genzyme.