Zytiga —The Next Step after Lupron?

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One of the unique characteristics of prostate cancer is its responsiveness to the withdrawal of testosterone. This “Achilles Heel” of prostate cancer was discovered in the 1940s when surgical removal of the testicles was shown to induce cancer remissions. In 1985, Lupron, an injectable medication that accomplished the same thing was approved by the FDA. Lupron works by tricking the testicles to shut down their production of testosterone.



Lupron controls prostate cancer for an average duration of two to six years in men with metastatic disease, and for more than ten years when treatment is started before metastatic disease is detectable on a scan. When Lupron stops working, other hormonal agents such as Casodex or Nilandron may provide temporary control, but their duration of effect (keeping the PSA down) usually lasts for less than a year.  

Controversy has raged in academia about whether a simple decline in PSA levels accurately indicates that a patient’s survival will be extended. So these days, the FDA will only approve a new drug if the pharmaceutical manufacturer documents improved survival in a prospective, placebo-controlled trial.  Proving improved survival is a much stiffer challenge than simply showing that a medication causes a temporary decline in PSA levels. 

Zytiga (abiraterone) which was studied in men with metastatic disease that had become resistant to Lupron proved this thesis—volunteers with metastatic, Lupron-resistant prostate cancer who received abiraterone were shown to live 33% longer than men who received a placebo.



Zytiga is a designer drug that works by exploiting the relatively recent 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. 

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

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