WEDNESDAY, Oct. 6, 2004 (HealthDayNews) -- The drugs docetaxel and estramustine can increase survival by a few months in men whose prostate cancer has spread to other parts of the body, two new studies find.
Progression of metastatic prostate cancer can be slowed initially by treatments that reduce levels of male hormones such as testosterone. As time goes by, however, cancer cells become resistant to this type of therapy. Once resistance sets in, doctors have little to offer these patients outside of palliative care, experts say.
But that may soon change.
"There has not been, until now, any treatment which has been shown to extend survival in these patients," said Dr. Ian Tannock, of the Princess Margaret Hospital and the University of Toronto. His team's study is "the first to show a small but definite improvement in survival."
The two studies appear in the Oct. 7 issue of the New England Journal of Medicine.
Despite advances in early detection, prostate cancer remains the second leading cancer killer of American men, according to the American Cancer Society. Even among men who get the disease while it is still confined to the prostate, between 30 percent to 40 percent will experience a recurrence in years to come, experts say.
Because prostate cancer cells depend heavily on testosterone to grow, reduction of circulating testosterone -- called hormone ablation therapy -- is often the first course of action in men who experience a recurrence of disease outside the prostate.
"Unfortunately, it's inevitable that these patients will relapse again after a period of time. And the problem is that there are, up until now, no viable therapies" for these hormone ablation-resistant cancers, said Donald J. Tindall, director of prostate cancer research at the Mayo Clinic, and co-author of a commentary in the journal on the subject.
In their study, Tannock's team examined the two-year survival of more than 1,000 men with ablation-resistant metastatic prostate cancer. They gave half the men standard palliative therapy (a combination of two drugs, mitoxantrone plus prednisone), while the other half received prednisone plus a relatively new drug, docetaxel (Taxotere).
"The overall improvement in survival, on average, was around three months" in patients taking docetaxel once every three weeks, Tannock said. He pointed out that this response varied among patients, with some responding minimally or not at all to the drug, while others responded well to docetaxel.
"In those who actually responded, added survival may be around six months," he said.
Overall, patients on the palliative regimen survived an average of 16.5 months, compared to an 18.9-month median survival for patients given docetaxel.
Docetaxel also helped drive down circulating prostate specific antigen (PSA), a measurement of prostate cancer activity, with nearly half of patients on the drug showing at least a 50 percent decline in PSA levels, the study found.
The drug did come with certain side effects, however, such as a loss of sensation in the fingers and toes. Nonetheless, more patients on the docetaxel regimen said they had significant reductions in pain and a better quality of life, compared with patients taking standard therapy, the researchers said.
Docetaxel works by targeting a specific molecule called tubulin, responsible for building tiny fibers that connect the nuclei of dividing prostate cancer cells.
"Docetaxel appears to attack this molecule, and thereby interferes with processes within [cancer] cells, including cell division," Tannock said.
A second study published in the journal found similar results. In that study, researchers led by Dr. Daniel P. Petrylak, of Columbia University in New York City, tracked the survival of 770 men with hormone ablation-resistant metastatic prostate cancer.
They found that men given docetaxel plus estramustine (Emcyt) -- another drug that targets tubulin -- achieved an average survival of 17.5 months, versus the 15.6 months averaged by men given standard palliative therapy.
Tindall said, "The take-home message here is that this is a small but significant step in our ability to treat hormone-refractory disease."
And it may only be the first step. Drugs such as docetaxel and estramustine "are known to inhibit some key cellular pathways," Tindall explained. "So I think that by understanding these cellular mechanisms in the refractory [cancer] stage, we have the potential of developing more therapeutic modalities" to fight the disease.
The Mayo Clinic's Dr. Jose D. Debes, who co-authored the commentary, said he shares Tindall's optimism.
"After the cancer fails to respond to androgen ablation and starts growing again, there are also a number of genes that become important," he said. These genes act on growth factors, proteins or receptors lying on the surface of cancer cells that can influence tumor spread.
"As more genes are identified, and more of these genes can be detected in particular patients, then you could use different therapies to target specific genes that might be over-expressed in these patients," Debes said.
The study by Tannock and his colleagues was funded by Aventis Pharmaceuticals, the maker of Taxotere. The study by Petrylak and his colleagues was supported by grants from the National Cancer Institute.
More information
For more on prostate cancer detection and care, visit the American Cancer Society.
