Testosterone Inactivating Pharmaceuticals
Hormonal therapy is a mainstay for Azure, Indigo, and Royal. The testosterone inactivating pharmaceuticals (TIP) fall into three broad categories:
Lupron-like medications work by blocking luteinizing hormone (LH) which comes from the pituitary gland. When LH levels in the blood are reduced, the testicles stop producing testosterone. There are two types of injectable drugs that block LH. The agonists, which are called Lupron, Eligard, Trelstar, and Zoladex. There is only one drug that works as an antagonist. It is called Firmagon.
Anti-androgen pills “block” testosterone activity without eliminating it from the blood stream. Anti-androgens are less potent but have fewer side effects, and are occasionally substituted for Lupron-like drugs in frail or elderly men. The trade names of the FDA-approved anti-androgens are Casodex, Flutamide and Nilutamide. Their generic names are bicalutamide, eulexin and nilandron.
Zytiga and Xtandi are FDA-approved medications for men who have become resistant to the “Lupron-like” medications. Zytiga also improves survival in men with High-Azure. Zytiga works in the cancer cell internally by blocking the synthesis of testosterone. Xtandi also works inside the cancer cell. It prevents testosterone from activating the androgen receptor that turns on cell growth. The side effects of Zytiga and Xtandi are similar to that of the Lupron-like drugs, with some exceptions.
Both the anticancer efficacy and the treatment-related side effects of TIP are increased by continuing the duration of treatment for a longer period. Therefore, the duration of TIP is adjusted in accordance with each individual’s specific situation. The following list presents eight ways that TIP is commonly used:
Men with High-Teal who are undergoing radiation often begin TIP two months before starting radiation and continue for a total of four to six months of therapy. Treatment for Low-Azure is similar to High-Teal.
Men with Basic-Azure and High-Azure who are undergoing radiation are typically treated with TIP for 18-24 months. Treatment starts two months before radiation and continues during and after the radiation.
Men with relapsed disease (Indigo) often receive intermittent TIP. This means that an initial course is continued for six to 12 months and then stopped. During the off-period, PSA levels are monitored every three months. A second cycle of TIP is initiated when the PSA rises to a prespecified level, usually between 3 to 6.
With occasional exceptions, men with Royal generally remain on TIP indefinitely.
Men with Royal who become resistant to Lupron are usually administered Xtandi or Zytiga. Treatment with Xtandi or Zytiga is continued until there is clear evidence of new metastases on a bone scan or body scan. A rising PSA by itself, without new metastatic lesions, is an insufficient rationale to stop Xtandi or Zytiga.
TIP has a potential role aside from its anticancer effects to shrink an enlarged prostate gland prior to a radioactive seed implant. Otherwise, some men with excessively large prostates would be ineligible for seed implantation.
TIP can be used as a primary therapy instead of surgery or radiation to treat men with Teal.
TIP can be used after surgery in men with Azure. This is controversial because older studies evaluating TIP for Teal after surgery showed no improvement in cure rates. However, those studies used only three months of TIP. Subsequent studies in Azure and Indigo using TIP for a longer duration show improved survival.
ABOUT THE AUTHOR
Mark Scholz, MD is the Executive Director of the Prostate Cancer Research Institute. He is also the Medical Director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers. He has authored over 20 scientific publications related to the treatment of prostate cancer.