The Use of Zytiga After Lupron to Control Prostate Cancer

One of the unique characteristics of prostate cancer is its responsiveness to the withdrawal of testosterone. This was discovered in the 1940s when surgical removal of the testicles was shown to induce cancer remission. In 1985, Lupron, an injectable medication that had a similar effect, was approved by the FDA. Lupron works by causing the testicles to shut down their production of testosterone.

Effectiveness

Lupron controls prostate cancer for an average duration of 18 to 24 months in men with metastatic disease. When Lupron stops working, other hormonal agents such as Casodex (bicalutamide) or Nilandron (nilutamide) may provide temporary control, but their duration of effect (keeping the prostrate-specific antigen (PSA) down) usually lasts for less than a year. 

Researchers have not established whether a simple decline in PSA levels accurately indicates that a patient’s survival will be extended. So new prostate cancer drugs can only be approved if the pharmaceutical manufacturer documents improved ​survival in a prospective, placebo-controlled trial. Proving improved survival is different than simply showing that medication causes a temporary decline in PSA levels. 

Zytiga (abiraterone acetate) is based on the discovery that resistance to Lupron (defined as cancer growth despite zero testosterone in the blood) is not a result of the cancer cells having learned to grow without testosterone. Rather, Lupron resistance is a result of prostate cancer cells having learned how to manufacture their own testosterone internally.

The anticancer effect of Zytiga works by blocking an essential enzyme located inside the cancer cell, an enzyme that is an integral component in the synthetic pathway of testosterone. The net result is that the cancer cell is blocked from manufacturing its own testosterone. 

Side Effects

Side effects of Zytiga can include changes in potassium levels in the blood, and in rare cases, liver dysfunction. It also enhances the action of cholesterol pills like Lipitor and Crestor, so their dosage needs to be reduced to compensate. It is occasionally associated with gastric irritation and stomach ulcers. Higher blood sugar levels can also occur in people who have diabetes.

To keep potassium levels in the normal range, Zytiga is administered in conjunction with prednisone, a form of cortisone. Cortisone can have side effects too.