BY MARK SCHOLZ, MD
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 1940’s when surgical removal of the testicles was shown to induce cancer remissions. In 1985, Lupron, an injectable medication that works by tricking the testicles into ceasing testosterone production, was FDA approved. Orchiectomy, or surgical removal of the testicles, has been declining in popularity ever since.
Lupron works for an average of 2-6 years in men with metastatic disease, and for more than ten years in men without metastasis. When Lupron stops working, other hormonal agents such as Casodex or Nilutamide are commonly employed. Their effectiveness is measured by monitoring prostate specific antigen (PSA). A good response is signaled by a declining level of PSA in the blood.
Controversy has raged in academia about the significance of these PSA responses and whether or not they are an indication of extended survival. Before approving new drugs, the FDA mandates that pharmaceutical manufacturers document improved survival in prospective placebo-controlled trials. A trial of abiraterone (Zytiga) in men with a rising PSA while on Lupron has shown just that—volunteers who received abiraterone lived 33% longer than men who received a placebo.
Zytiga is a designer drug that exploits the relatively recent discovery that cancer progression is a result of prostate cancer cells manufacturing their own testosterone instead of feeding on testosterone originating from the testicles and reaching the prostate cancer cells via the bloodstream. Zytiga works inside the cancer cell by blocking the function of an essential enzyme in the synthetic pathway of testosterone. On April 28, 2011, the FDA approved Zytiga, a product of Centocor Ortho Biotech which is owned Johnson & Johnson. We have conducted one phase early access protocol (EAP) and two phase III trials of abiraterone in our Marina del Rey office.
Side effects of Zytiga can include changes in potassium levels in the blood and rare cases of liver irritation. Zytiga has to be administered with prednisone, a form of cortisone. Cortisone can be associated with gastric irritation and occasionally stomach ulcers. People with diabetes may experience higher blood sugar levels.
Since Zytiga will be offered at a cost of $5,000.00 per month, many men will be interested to know that its chemical mechanism of action is very similar to another more affordable medication already on the market—ketoconazole. And a month’s supply ketoconazole is only $60.00. However, there has been subdued enthusiasm for ketoconazole due to a very high frequency of adverse interactions with other common medications like Lipitor, Zithromax, Norvasc, Glipizide, Paxil, Prozac, Coumadin, Coreg and antihistamines. It can also cause side effects such as stomach upset or liver problems. To be used safely, close monitoring on therapy is essential. Even so, if used cautiously, after close to 20 years of experience with ketoconazole, I have found that many men can tolerate it quite well.
For men who can afford it, or at least have insurance to cover the cost, Zytiga will be popular thanks to the much lower incidence of side effects. Even with the major cost considerations I predict Zytiga will become the standard of treatment for men who are resistant to Lupron. And just as Lupron is continued indefinitely, even after PSA begins to rise, Zytiga will probably be used indefinitely as well, even if the cancer is progressing. After all, now that we know that Zytiga can deny the cancer cells the capacity to manufacture their own testosterone, why would we want to stop the medicine and allow those out-of-control cells to start producing testosterone again?