The development and FDA approval of the new anti-androgens, Zytiga (abiraterone), Xtandi (enzalutamide) and Erleada (apalutamide), represent a major advance in prostate cancer treatment. This issue provides you with experts’ current views on the use of these agents.

For hormone resistant metastatic prostate cancer, their use is now well established. They can provide an alternative to Taxotere (docetaxel) chemotherapy in patients who have failed initial hormonal therapy. While most patients will eventually experience cancer progression on these agents and need chemotherapy, the delay in initiating chemotherapy prolongs the period they have with better quality of life.

Recent trials have extended the use of these drugs to patients with nonmetastatic hormone resistant disease. These studies have shown that early use of these drugs results in a rather dramatic delay in the appearance of metastatic disease. As a result, early use of these agents is becoming wide spread.

However, Dr. Mario Eisenberger does an excellent job of discussing unresolved issues with the early use of these drugs. I agree with him that we need to be concerned about long-term side effects of these drugs as many men are likely to be on them for more than five years. For example, Zytiga (abiraterone) results in a rapid drop in both testosterone and estradiol. As estradiol plays a major role in bone health, it is possible that long-term use of Zytiga (abiraterone) might increase the risk of fractures.

The current trend in clinical trial design is to test drugs in all patients who clinically fit the protocol. Thus, all men with hormone resistant metastatic disease would be tested with Zytiga (abiraterone) or Xtandi (enzalutamide). Dr. Eleni Efstathiou correctly points out that a portion of these patients’ cancers may already have molecular changes that make them likely to respond poorly to these drugs. She is investigating whether testing for these molecular changes will allow clinicians to select patients likely to have a significant and durable response to treatment. This approach makes sense.

As a practical matter, these new drugs are important enough that you, as a patient, want to make sure that the doctor managing your prostate cancer is knowledgeable and experienced in the use of these drugs.

Charles E. Myers, Jr., MD