The FDA ( Food and Drug Administration ) has approved Zytiga ( Abiraterone acetate ), an oral, once-daily medication for use in combination with Prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing Docetaxel.

Androgens are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can help fuel the tumor’s growth. Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumor tissue is an additional source of androgens.
Zytiga is an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.

Zytiga, in combination with Prednisone, was evaluated in a phase 3, randomized, placebo-controlled, multicenter clinical study in patients who had received prior chemotherapy containing a taxane ( n=1,195 ).
Patients were randomized 2:1 to receive Abiraterone 1 gram daily in combination with Prednisone 5 mg twice daily or placebo in combination with Prednisone 5 mg twice daily ( control arm ).

Results of the pivotal phase 3 study showed that at pre-specified interim analysis, treatment with Abiraterone in combination with Prednisone resulted in a 35% reduction in the risk of death ( 14.8 months vs 10.9 months; hazard ratio, HR=0.646; p<0.0001 ) and a 3.9 month difference in median survival compared to placebo plus Prednisone.
In an updated analysis, results were consistent with those from the interim analysis with a 4.6 month difference between the two arms in median survival ( 15.8 months vs 11.2 months; HR=0.74 ).

The most common adverse reactions ( greater than or equal to 5% ) reported in the clinical study were: joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection.

Safety information

Contraindications - Zytiga may cause fetal harm and is contraindicated in women who are or may become pregnant.

Warnings and Precautions

Hypertension, hypokalemia and fluid retention due to mineralocorticoid excess - Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in hypertension, hypokalemia and fluid retention. Safety has not been established in patients with LVEF less than 50% or NYHA Class III or IV heart failure. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency has been reported in clinical trials after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency if Prednisone is stopped or withdrawn or if the patient experiences unusual stress. Perform appropriate tests, if indicated, to confirm adrenocortical insufficiency. Increased dosages of corticosteroids may be used before, during and after stressful situations.

Hepatotoxicity - Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function and modify, withhold or discontinue Abiraterone dosing as recommended.

Food Effect - Zytiga must be taken on an empty stomach. Exposure of Abiraterone increases up to 10-fold when Abiraterone acetate is taken with meals. No food should be eaten for at least two hours before the dose of Zytiga is taken and for at least one hour after the dose of Zytiga is taken.

Drug interactions

Abiraterone is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. Additionally, Abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.

Source: Centocor Ortho Biotech, 2011

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