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 testerone. 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.

white pills coming out of medicine bottle
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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 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 medication causes a temporary decline in PSA levels. 

Zytiga is given in combination with Lupron post-Lupron failure and not alone.

Zytiga is a designer drug that works by exploiting 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.

Its 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

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.

6 Sources
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  1. Wadosky KM, Koochekpour S. Therapeutic rationales, progresses, failures, and future directions for advanced prostate cancerInternational Journal of Biological Sciences. 2016;12(4):409-426. doi: 10.7150/ijbs.14090

  2. Federal Register. Determination That LUPRON (Leuprolide Acetate)Injection, 1 Milligram/0.2 Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness.

  3. American Society of Clinical Oncology. Prostrate Cancer: Types of Treatment.

  4. National Cancer Institute. Prostrate-Specific Antigen (PSA) Test.

  5. Federal Drug Administration. Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products Guidance for Industry.

  6. Janssen Biotech. Potential Zytiga Side Effects.