General Information

Zytiga (abiraterone acetate) is an orally active inhibitor CYP17 a cytochrome p450 complex that is involved in testosterone production.

Zytiga is specifically indicated in combination with prednisone for the treatment metastatic castration-resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer.

Zytiga is supplied as a tablet for oral administration. The recommended dose is:

• Metastatic castration-resistant prostate cancer: 1,000 mg orally once daily with prednisone 5 mg orally twice daily
• Metastatic castration-sensitive prostate cancer: 1,000 mg orally once daily with prednisone 5 mg orally once daily

Mechanism of Action

Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 a-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.

Side Effects

Adverse events associated with the use of Zytiga may include, but are not limited to, the following:

• joint swelling or discomfort
• hypokalemia
• edema
• muscle discomfort
• hot flush
• diarrhea
• urinary tract infection
• cough
• hypertension
• arrhythmia
• urinary frequency
• nocturia
• dyspepsia
• upper respiratory tract infection

Clinical Trial Results

The FDA approval of Zytiga was based on a randomized, placebo-controlled, multicenter study in 1,195 subjects. The subjects received either Zytiga orally at a dose of 1,000 mg once daily in combination with prednisone 5 mg orally twice daily or placebo once daily plus prednisone 5 mg orally twice daily. Treatment was administered until disease progression (defined as a 25% increase in PSA over the patient’s baseline), initiation of new treatment, unacceptable toxicity or withdrawal. The pre-specified interim analysis was conducted after 552 deaths and showed a statistically significant improvement in overall survival in subjects treated with Zytiga compared to placebo. An updated survival analysis was conducted when 775 deaths occurred. Results from this analysis were consistent with those from the interim analysis. In the interim analysis the median survival was 14.8 months for the Zytiga arm and 10.9 months for the placebo arm. In the updated analysis the median survival was 15.8 months and 11.2 months, respectively.