ASCO PROSTATE: Docetaxel-Based Therapy Viewed for Refractory Prostate Cancer

KISSIMMEE, Fla., Feb. 26 -- Docetaxel (Taxotere)-based combination therapy using is being investigated in a dozen trials for hormone refractory prostate cancer, investigators reported here.

During an industry-sponsored satellite symposium held in conjunction with a prostate cancer symposium here, the investigators said there were four phase III docetaxel-based combination trials and eight phase I and II trials.

In the symposium titled, "Improving Upon Current Standards: The Integration of Novel Therapies in the Treatment of Androgen-Independent Prostate Cancer," sponsored by Novacea, Howard Scher, M.D., chief of the Genitourinary Oncology Service at the Memorial Sloan-Kettering Cancer Center in New York described a number of these trials.

Dr. Scher said the ongoing phase III studies include trials of docetaxel in combination with bevacizumab (Avastin), DN-101 (calcitrol), atrasentan; GVAX; and VEGF-trap compounds.

He suggested that when doctors consider whether to prescribe certain treatments, "it may be time we focus less on statistical significance alone, and more on patient benefit." He noted, for example, that just-released data from a trial of satraplatin plus prednisone did not confirm a survival benefit, but did suggest that the combination was effective against pain, which appeared to translate into a slowing in progression of clinical symptoms.

He said, too, that many researchers are shifting focus from statistical significance alone to outcomes that are softer and more difficult to measure.

In another presentation at the symposium, Christopher Logothetis, M.D., professor and chair of Genitourinary Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston, said that PSA screening of prostate cancer continues to be dogged by a "high rate of true negatives," leading many potentially unneeded biopsies. The diagnosis-management problem extends, he said, into the assessment of metastases. "The ability to adapt to locate the lethal from the non-lethal metastasis has to improve," he said.

Dr. Logothetis also addressed issues of treatment toxicity and discussed options to improve bone mineral density for patients receiving androgen deprivation therapy.

A third speaker, Tomasz M. Beer, M.D., associate professor of medicine at the Oregon Health and Science University, suggested that doctors should take another look at the role of vitamin D in prostate cancer. He demonstrated that patients who lack, or are lacking in vitamin D, tend to die quicker from many cancers.

"In these studies it seems that a person with a good source of vitamin D is less like to die from cancer or even get cancer than a person who is lacking in vitamin D," he said.

He also explained that "it appears that patients react better from cancer treatment in the summer months than in the fall or winter months." He discussed studies in which docetaxel was combined with calcitriol. In the studies patients once again showed more improvement in the summer months while using this combination, than in the winter months.

Charles Drake, M.D., assistant professor of medical oncology, immunology, and urology at the Johns Hopkins Kimmel Cancer Center in Baltimore, discussed the future of prostate cancer vaccines.

Dr. Drake focused on the notion of the inability of patients to develop CD8 T-Cells or to activate them in the defense of the body against a cancer. "There is a population of CD8 T-Cells armed and ready to go in the body, but are being held back. If we can free up those T-Cells sooner than we currently are the patient maybe able to fend off further cancer cell development."

Dr. Drake also cited the role in cancer of immature dendritic cells. "These cells are like teenagers, in that they eat up everything in sight." He suggested that scientists would be able to use immunotherapy as a treatment option in the near future.

Dr. Logothetis did not list any potential conflicts of interest. Dr. Beer listed his potential conflicts of interest as a consultant or advisor for Berlex, Dendreon and ImClone; stock ownership in Novacea; research funding from sanofi-aventis, OSI, Inc., Dendreon Corp., Pfizer, Praecis, Medarex and Genzyme. Dr. Sher reported that he receives grants and research support from Novartis, Novacea, Bristol-Myers Squibb and sanofi-aventis. Dr. Drake reported that he receives grants and research support from Cell Genysis; consultant fees or stock ownership from Novacea; and is part of the sanofi-aventis speaker's bureau.