A new drug with a radically different way of attacking prostate cancer has done well in an initial trial and is ready for larger-scale testing, researchers report.
One standard treatment for the malignancy is to inhibit the activity of androgens, male hormones such as testosterone that help drive tumor growth. Existing anti-androgens try to “shut down the factory” that produces the hormones, but the new drug blocks the receptors for those androgens on the tumor cells, said Dr. Howard I. Scher, chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer Center in New York City and co-author of a report to be published online by the journal Science.
“There is a lot of interest in the drug, because the preliminary results are very promising,” Scher said.
The report in the journal describes the results of the treatment of 30 men with advanced prostate cancer that was not responding to conventional anti-androgen therapy. After treatment with the drug, there were “sustained declines” in blood levels of prostate specific antigen, a biomarker of tumor growth, in 13 of the 30, or 43 percent, which the report called a “promising” result.
The researchers now have data on 114 men given the drug, Scher said. “It showed not only declines in PSA but also regression of the tumor on scans and also that circulating tumor cell counts, another measure of treatment, converted from unfavorable to favorable in a considerable percentage of patients,” he said.
Based on those results, Scher said, an application for a large-scale trial has been submitted to the U.S. Food and Drug Administration by Medivation Inc., a California-based biopharmaceutical company that has licensed the drug, now called MDV3100. The hope is that the trial will lead to FDA approval of the drug for clinical use.
The trial would be international in scope, he said, but the length and size have not been determined.
MDV3100 came out of research done at the University of California, Los Angeles, by Dr. Charles L. Sawyers, a cancer biologist who now is chairman of the human oncology and pathogenesis program at Sloan-Kettering.
“My laboratory was studying why men develop resistance to current anti-androgen drugs,” Sawyers said. “We found that resistant tumors have higher levels of androgen receptors. What we showed was that cells, by making more of these receptors, can escape those drugs. Based on that, we developed a cell line that made higher levels of receptors and used that as a screen for compounds that could block the receptors.”
Sawyers did the research in collaboration with a group led by Michael Jung, a chemist at UCLA. “We had some ideas about what chemical structures we might need to get such a result,” Sawyers said. “His group synthesized a set of compounds, my group screened them, and over the months, we learned what to do. There were a number of chemicals known to bind to a receptor with different affinities, and we made derivatives of them.”
That work produced more than one effective receptor blocker. MDV3100 was selected as the most promising.
Though the immediate goal is to get FDA approval for use of the drug in men whose prostate cancers do not respond to existing anti-androgen therapy, the ultimate hope is that it could be used for first-line therapy, Scher and Sawyers said.
“That is a typical scenario,” Sawyers said. “First you test it in late-stage patients. If it is effective there, you would want to move it to front-line therapy.”
About half of all prostate cancers have the overgrowth of androgen receptors that MDV3100 is designed to attack, Scher noted.
Side effects do not appear to be a problem, Sawyers said. “At high doses, fatigue has been a problem in some men — higher doses than are needed to get benefit,” he said.