1. Carlson, Robert H.

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CHICAGO-A new treatment option for men with castration-resistant prostate cancer may be in the works, if results from the recent ARMOR1 trial of the small-molecule oral drug galeterone (TOK-001) bear out. The Phase I study (Abstract CT-07), presented at the American Association for Cancer Research Annual Meeting, showed that almost half of the 49 patients had a 30% or greater reduction in PSA levels, and 11 (22%) of those had a 50% or greater reduction.

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Galeterone is unique in that it has three mechanisms of action:


* Inhibition of CYP17 lyase activity and blockade of the androgen receptor.


* Reduction of levels of the ligand that binds to the receptor.


* Degradation of the androgen receptor protein.



Drugs are currently available for the second and third mechanisms, explained the study's co-lead investigator, R. Bruce Montgomery, MD, Associate Professor of Medical Oncology at the University of Washington School of Medicine in Seattle, speaking at a news conference at the meeting that highlighted late-breaking research.


"Simple hormone therapy lowers testosterone levels, for example, but hormone therapy doesn't work very well in the tissue. And bicalutamide can block the receptor, but it's not a very good antagonist."

Galeterone... - Click to enlarge in new windowGaleterone

Inhibition of CYP-17 lyase is "more than a little novel in this setting," he added.


In the dose-escalation trial, 49 patients were randomly selected to receive one of eight dose escalation cohorts of galeterone daily for 12 weeks. After that, eligible patients could continue treatment in an extension phase.


In early efficacy tests, about half of the patients (49%) had reductions in PSA of 30 percent or more, and 11 (22%) of those patients had reductions of 50 percent or more.


The moderator of the news conference, Jose Baselga, MD, PhD, Associate Director and Chair and Chief of Hematology/Oncology at Massachusetts General Hospital Cancer Center, commented that galeterone clearly has activity but this was a very early trial.


"There is still a question of whether and how galeterone will be different from other new drugs for advanced prostate cancer, such as MDV3100 or abiraterone. But clearly galeterone has multiple mechanisms of action, and they've seen activity-that's important."


Montgomery noted that a Phase II study of long-term safety and efficacy is now being planned for later this year by Tokai Pharmaceuticals.