A new therapy for metastatic prostate cancer has shown considerable promise in early clinical trials involving patients whose disease has become resistant to current drugs.
 
Chemists and biologists at UCLA and colleagues at several other institutions, including Memorial Sloan-Kettering Cancer Center, have created a new drug to treat a particularly lethal form of the disease, known as castration-resistant prostate cancer, or CRPC. Also referred to as hormone-refractory prostate cancer, CRPC is resistant to further treatment by anti-hormone drugs such as Casodex and Eulexin.
 
In an article, the scientists describe the development and testing of two novel compounds, MDV3100 and RD162, which block the androgen receptor (AR) in CRPC cells, and report results from clinical trials in which MDV3100 was found to lower prostate-specific antigen (PSA) levels — a marker for tumor growth — in men with CRPC.
 
The new, small organic molecule MDV3100 was ‘designed as a very strong antagonist of the androgen receptor to stop the growth of any prostate cancer that requires the AR for propagation, which includes most forms of prostate cancer,’ said Michael Jung, UCLA professor of chemistry and biochemistry and a researcher at UCLA’s Jonsson Comprehensive Cancer Center, whose research group synthesized both MDV3100 and RD162.
 
The biology research was carried out in the UCLA departments of medicine, urology and pharmacology by Charles Sawyers and his research group; Sawyers has since moved to Memorial Sloan-Kettering Cancer Center in New York, where he serves as chair of the human oncology and pathogenesis program. The UCLA patents for both compounds were licensed by the pharmaceutical company Medivation Inc., which chose to test MDV3100 in clinical trials.
 
The drug has successfully completed Phase 1 and Phase 2 clinical trials, and the Food and Drug Administration has agreed to allow Medivation to begin what Jung described as ‘the pivotal Phase 3 clinical trials.’
 
The results of clinical studies with the MDV3100 drug, at 240 mg once a day, was very effective at lowering PSA levels, and also in reducing the number of circulating tumor cells, without any significant toxicity.
 
‘I think it is quite likely that the exciting results seen in the smaller population will also be evident in the larger Phase 3 trial and that the drug could be approved for use in the next few years,’ said Jung, who is also a member of the California NanoSystems Institute (CNSI) at UCLA.
 
Of 30 men with anti-androgen–resistant prostate cancer who received low doses of MDV3100 in the multisite Phase 1/2 trial designed to evaluate safety, 22 showed a sustained decline in PSA levels, an indication that their cancer was responding favorably to the drug. This trial is still underway, and results from a total of 140 patients receiving higher doses of the drug will be reported within the next year, Sawyer said.
 
The Phase 3 clinical trial will evaluate the drug’s effect on survival in a large group of patients with metastatic prostate cancer.

Release Date: April 9, 2009
Source: University of California – Los Angeles