ATLANTA, GA USA (UroToday) - At this year's American Urological Association (AUA) Annual Meeting in Atlanta, Dr. Judd Moul presented a practice management perspective on the burden of metastatic castrate-resistant prostate cancer (mCRPC), the mechanism of action for Zitiga® (abiraterone acetate), as well as phase III clinical evidence. He fielded nearly 30 minutes of questions from more than 400 participants. His AUA audio report recaps highlights and several key findings. The following are highlights from an interview with Dr. Moul based on his May 21, 2012, AUA Clinical Theater presentation
Background: In mCRPC, prostate tumor cells remain androgen-sensitive by several mechanisms and the new terminology of mCRPC aptly reflects the evidence that in mCRPC the tumor remains hormone sensitive. Abiraterone inhibits the CYP17 enzyme complex required for androgen biosynthesis in the testicular, adrena,l and prostatic tumor tissue.
Q: What are the key points clinicians should consider when using abiraterone acetate for the treatment metastatic castration-resistant prostate cancer (mCRPC) following treatment by docetaxel with prednisone?
Dr. Moul: As physicians use abiraterone acetate (market name Zytiga®) a couple of key points come up: How do you sequence this drug? At the current time, this drug is to be used after a patient has progressed on docetaxel- (Taxotere®) based chemotherapy. Then the question would come up, you start Zytiga and the patient has responded, how do you know when to discontinue this drug?
It’s important to point out for the clinician, In the clinical trial where Zytiga was FDA approved, the trial did not base the discontinuation on PSA alone. The patients had to have met three criteria for disease progression before abiraterone acetate was stopped. First, they had to have a 25% increase in their PSA levels over baseline when they started the drug. Second, they had to have radiographic progression (bone scan, CT scan or MRI had to show worsening of the disease). Third, they had to have symptomatic or clinical progression as defined by the physician.
From a urology standpoint we certainly know patients follow their PSA. We follow PSA and rely on PSA; however, we encourage doctors using this drug not to simply stop the drug solely based on PSA progression as well as educating our patients about how to define success and progression with this product.
Dr. Moul: In summary, key takeaway messages about abiraterone acetate are:
- Abiraterone acetate inhibits CYP17, an enzyme complex needed for androgen biosynthesis, and when used in combination with prednisone improved the overall survival in patients with mCRPC who received prior chemotherapy containing docetaxel.
- In the latest analysis of the clinical trial, there was a 4.6 month survival difference comparing Zytiga to prednisone alone. That is quite impressive considering these patients had all progressed after docetaxel. This is a very advanced, difficult patient population, yet Zytiga was improving the median survival by 4.6 months.
- The safety profile (for abiraterone acetate) is quite tolerable and quite good. From a testing standpoint and a clinical management standpoint (during CYP17 inhibition, since the cortisol production is blocked) there is the potential for this drug to drive this pathway toward mineralocorticoid excess.
- From a board exam and clinical management perspective, this drug can sometimes cause hypokalemia (low potassium), hypertension, or fluid retention. These are the three key side effects considered potentially unique based on the drug’s mechanism of action.”
Judd W. Moul, MD, FACS is the James H. Semans, MD, Professor of Surgery and Director of the Duke Prostate Center, Duke Cancer Institute and Division of Urology at the Duke University Medical Center, Durham, NC. Prior to joining Duke, Dr. Moul was the professor of surgery at USUHS in Bethesda, MD, an attending urologic oncologist at the Walter Reed Army Medical Center, and a former director at the Center for Prostate Disease Research. Dr. Moul currently serves on the editorial boards of Prostate Cancer and Prostatic Diseases, Prostate Cancer, BJU International, American Journal of Men’s Health, Brazilian Journal of Urology, and World Journal of Urology. He has authored over 500 medical and scientific manuscripts and book chapters and lectured at U.S. and International meetings.
Interview conducted at the American Urological Association (AUA) Annual Meeting - May 19 - 23, 2012 - Georgia World Congress Center - Atlanta, GA USA
