Neoadjuvant use of abiraterone in localized high-risk prostate cancer shows significant benefits in pathologic response.

Presurgical use of abiraterone in localized high-risk disease shows significant benefits.

Six months of treatment with the targeted drug abiraterone (Zytiga; Janssen Biotech, Johnson & Johnson) and standard androgen deprivation therapy prior to radical prostatectomy eliminated or nearly eliminated cancer in one third of men with localized high-risk prostate cancer, a phase II study has shown.

The findings also demonstrate that abiraterone blocks production of testosterone and related metabolites in tumor cells themselves; it doesn't simply lower levels of these androgens in the blood.

“This is an exciting new step forward” because the drug is usually prescribed for men with advanced, metastatic prostate cancer, remarked Nicholas Vogelzang, MD, a medical oncologist at Comprehensive Cancer Centers of Nevada. Vogelzang, chair of the American Society for Clinical Oncology's (ASCO) Cancer Communications Committee, moderated a May 16 press conference highlighting the findings.

Men with localized high-risk prostate cancer have a poor prognosis, even with aggressive treatment. These men generally have a prostate-specific antigen level above 20 ng/mL, a Gleason score of 8 or higher, and disease throughout the prostate.

Knowing that testosterone often fuels prostate cancer, researchers have studied the use of androgen deprivation therapy, such as leuprolide (Lupron; Abbott), to limit testosterone production prior to surgery in men with localized high-risk prostate cancer. Unfortunately, this treatment has yielded limited benefits.

This new study evaluated the effect of adding abiraterone, an oral drug that inhibits androgen production, to a standard leuprolide injection regimen prior to surgery. Among a group of 24 men who received 24 weeks of abiraterone, 34% experienced a complete or nearly complete pathologic response, meaning that their tumors were eliminated or shrank to 5 mm or smaller. In a second group of 27 men who received abiraterone for only 12 weeks, the response rate was 15%.

“For this proportion of patients with high-risk disease to have very little to no detectable cancer in the prostate after 6 months of therapy is dramatic,” said Mary-Ellen Taplin, MD, an oncologist at Dana-Farber Cancer Institute in Boston, associate professor of medicine at Harvard Medical School, and the study's lead author. She noted that the normal response rate to neoadjuvant androgen deprivation therapy is just 5%.

Recent research has shown that prostate tumors can evade the effects of androgen deprivation therapy by making the testosterone and other androgens they need to keep growing. Taplin said that men in the study all had a prostate biopsy 12 weeks before surgery to assess androgen levels inside tumor cells.

The data showed that abiraterone very effectively lowers intracellular levels of all the androgens it's designed to suppress, not just the serum levels. “No one has ever demonstrated this at a cellular level,” said Taplin, who will present the findings at ASCO's 2012 Annual Meeting in Chicago on June 2. “It's really cool data.”