A new drug called MDV3100 has shown significant promise in lowering the prostate specific antigen (PSA) levels ‑ a marker for tumor growth ‑ in men with advanced prostate cancer who have no other option for cure. The drug has also been shown to shrink prostate cancer lesions seen on imaging studies.  The Oregon Health & Science University Knight Cancer Institute is one of just four centers worldwide to enroll participants in a Phase I/II clinical trial that contributed to this discovery.

The findings are described in a new study published in this week’s Science Express, the online version of the journal Science.

“We are encouraged by the benefits participants are experiencing from this research,” said Tomasz Beer, M.D., OHSU principal investigator, director of the Prostate Cancer Research Program and deputy director of the OHSU Knight Cancer Institute. “This clinical trial is yet another example of how the OHSU Knight Cancer Institute is able to consistently bring the most exciting and promising new drugs and treatment options to Oregonians. Patients no longer need to travel anywhere else in the world to receive the latest, most state-of-the-art cancer care.”

Current treatments for men with metastatic prostate cancers inhibit the activity of male hormones that help drive tumor growth. Many of these drugs disrupt the androgen (male hormone) receptor, which helps regulate cell proliferation. But tumors eventually become drug-resistant by expressing higher levels of androgen. This overexpression contributes to the development of a more aggressive form of the illness called castration-resistant prostate cancer, or CRPC.

Armed with this knowledge, the study’s lead investigator, Charles Sawyers, M.D., chairman of human oncology and pathogenesis at Memorial Sloan-Kettering Cancer Center (MSKCC), and chemist Michael Jung, Ph.D., at UCLA, collaborated to review a number of compounds to determine which compounds could most effectively block the androgen receptor.

Two of the compounds evaluated, MDV3100 and RD162, were found to work well in cells in culture, shrink tumors in prostate cancer mice models, maintain tumor shrinkage for months, and prevent the androgen receptor from activating additional genes later in the process. Currently approved drugs cannot disable the receptor in this way.

In light of these discoveries, the biopharmaceutical company Medivation, Inc., licensed RD162 and MDV3100 from UCLA 2006, and, in 2007, the OHSU Knight Cancer Institute and other sites began enrolling men with CRPC who had relapsed after treatment with conventional hormone therapy in phase I/II clinical trials of MDV3100.

Of the 30 men who initially received low doses of MDV3100, 22 showed declining PSA levels, and 13 of the 30 men (43 percent) had PSA levels fall by more than one-half. Further positive results from an additional 110 study participants with metastatic CRPC who received MDV3100 at higher doses recently was reported at the ASCO Genitourinary Cancers Symposium in February 2009 (see abstract: www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=64&abstractID=20500).

A larger trial of MDV3100 is planned later this year. The Phase III study will investigate the drug’s effect on cancer survival, and the OHSU Knight Cancer Institute will again participate.

Researchers at MSKCC, UCLA, OHSU, University of Washington, Seattle, and Medivation, Inc., contributed to the research, which was led by investigators at MSKCC and conducted through the Prostate Cancer Clinical Trials Consortium, which is sponsored by the Department of Defense and the Prostate Cancer Foundation.