MDV3100 Shown to Be Safe and Effective for Treatment of Prostate Cancer

A Phase 1-2 clinical trial has established the maximum tolerated dose of the compound MDV3100, a promising drug candidate for the treatment of castration-resistant prostate cancer (CRPC)--once known as or androgen-independent (androgen-resistant) prostate cancer.

MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and coactivator recruitment of the ligand-receptor complex. It also induces tumor cell apoptosis and has no agonist activity. Since growth of CRPC is dependent on continued androgen-receptor signaling, investigators at Memorial Sloan-Kettering Cancer Center (New York, NY, USA) assessed the antitumor activity and safety of MDV3100 in men with this disease.

They reported in the April 24, 2010, issue of the journal the Lancet that all the 140 patients who were treated with doses of MDV3100 ranging from 30 mg to 600 mg daily showed some antitumor response as measured by PET imaging, bone scans, and blood tests.

These positive responses included a decline in PSA (prostate-specific antigen) of at least 50% in more than half of the patients and tumor regressions in 22% of the patients. Overall, two-thirds of patients had partial remissions or stable disease in tumors that had spread to soft tissue or bone. At the maximum tolerated dose for sustained treatment (240 mg per day for 28 days), the number of circulating tumor cells fell in 49% of patients and 91% of patients who initiated therapy with favorable counts retained favorable counts during treatment. The drug was generally well tolerated, with nausea, constipation, diarrhea, and anorexia being the most common mild side effects reported. The most frequently reported serious side effect at higher doses was fatigue, which generally resolved after dose reduction.

"We were encouraged to see antitumor activity in men whose disease had spread to other parts of the body after either becoming resistant to previous hormone treatments or progressing following chemotherapy,” said first author Dr. Howard Scher, professor of oncology at Memorial Sloan-Kettering Cancer Center. "These findings strengthen the drug's potential to change the outlook for a group of patients who currently have limited effective treatment options from which to choose.”

Due to the positive outcome of the Phase 1-2 study, a multinational randomized Phase 3 clinical trial has begun to examine MDV3100 versus a placebo for the treatment of men with advanced prostate cancer who were previously treated with chemotherapy.

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Memorial Sloan-Kettering Cancer Center