A New Generation of Therapies for Prostate Cancer

Dan George, MDDan George, M.D., is a medical oncologist and director of Duke Cancer Institute Genitourinary Oncology. He and his colleagues at Duke are continually working to offer better treatment options to men with prostate cancer.

What is the outlook for men with prostate cancer?

Today we are able to help men continue to live with prostate cancer for years beyond what we’ve historically been able to do. Even for patients with metastatic disease, we can offer a sequence of therapies that in many cases can stop the cancer from progressing and can maintain quality of life for years.

Prostate cancer is different from many other cancers in its dependency on testosterone. Traditionally, therapies that suppress testosterone production by the testicles have been a mainstay of treatment for advanced disease. But recently it has been shown that prostate cancer can progress despite low testicular testosterone because the tumor is either able to make its own testosterone or turn on the testosterone receptor in the tumor. Now we have this new generation of therapies that target testosterone production anywhere in the body, particularly in the tumor itself. One of those therapies is abiraterone acetate, which was approved in 2011 by the Food and Drug Administration for use in men with what we now term metastatic, castration-resistant prostate cancer. In addition, we have a unique androgen receptor antagonist, enzalutamide, approved in 2012, that blocks the testosterone receptor in a way that no other drug has been able to; it blocks not only the receptor’s ability to bind testosterone but also prevents further activation steps. These drugs have drastically improved the survival of men with metastatic, castration-resistant prostate cancer.  

Can these new treatments help men with earlier-stage disease?

Right now these drugs are approved for use in metastatic, castration-resistant disease, but at Duke we are studying these new therapies to understand how well they will work in men with earlier stagedisease, how they work in combination with other therapies, and whether some patients will benefit more than others. Patients at Duke can participate now or in the near future in five different clinical trials of these new therapies.These trials will enable patients, including men with early-stage disease, to get early access to new combinations of these therapies. [/pullquote]These trials will also improve our understanding of how best to use these drugs to help prevent relapse in a wider group of men.

Describe the trials offering enzalutamide to a wider range of men.

Two trials will look at different ways of using enzalutamide in men with early stage prostate cancer. One of these has just opened at Duke, and it pairs enzalutamide with traditional hormonal therapy and radiation therapy, to test if this combination can induce a complete remission in men who have already had their prostate removed and who have residual cancer (detected by a rising PSA, or prostate specific antigen level). This trial is led by Andrew Armstrong, MD, at Duke and is offered only to patients at Duke and at MD Anderson Cancer Center.

Another study combines enzalutamide with traditional hormonal therapy in men who have had either surgery or radiation therapy to treat prostate cancer and have recurrent cancer (detected by a rising PSA level). We hypothesize that the combination will delay the time before patients become resistant to traditional hormonal therapy alone, which is the standard of care for these men. This study will test a rigorous exercise regimen for some men, to find out if we can improve cardiopulmonary fitness and quality of life by maximizing muscle strength and endurance. When this study opens in the second half of 2014, it will provide an opportunity for our patients to get early access to this combination of enzalutamide and traditional hormone therapy. This trial is led by Michael Harrison, MD at Duke and will be open to patients only at Duke and at Memorial Sloan Kettering Cancer Center.

What trials at Duke involve abiraterone?

For men with newly diagnosed prostate cancer who have selected a radiation and hormonal therapy approach, we are testing a combination of abiraterone with radiation therapy and traditional hormonal therapy. Our study tests a more potent combination of hormonal therapy but for a shorter period of time than the standard of care hormones. Led by Bridget Koontz, MD, at Duke, this trial is available only to patients at Duke and at MD Anderson Cancer Center.

We are also participating in a national phase 3 trial that studies the combination of enzalutamide, abiraterone, and prednisone compared to enzalutamide alone to find out if the combination improves survival in patients with castration-resistant, metastatic prostate cancer. This study is available across the country and led by the Alliance Cooperative Group. Andrew Armstrong, MD, from Duke is the correlative science leader, and Susan Halabi, MD, from Duke is the statistical chair. Finally, we are examining differences in men’s responses to abiraterone according to their race and genetics. There is some evidence that African-American men may respond better to this drug than the general population. We’re looking to test this hypothesis and will evaluate the response to this drug in 50 African-American men and 50 Caucasian men with metastatic, castration-resistant prostate cancer. Through this study, we will explore genetic markers that may explain any differences in response. I am the lead investigator for this study, and it is enrolling patients at Duke and at some of our partners in the Duke Cancer Network.

For more information about these trials, visit Duke Clinical Trials.