Hormone Refractory Disease

Patients who present with advanced or metastatic disease or those who suffer a disease relapse following definitive localized therapy are most commonly placed on hormone therapy. Prostate cancer cells are responsive to the male hormone, testosterone. Removal of testosterone will cause some prostatic cancer cells to die, while the remainder stop their growth and become dormant (a sort of hibernation). While nearly 90% of patients will respond favorably to removal of male hormone (commonly termed hormonal ablation), this treatment will eventually fail to control cancer growth. On average the relapse can occur within 3-4 years but can take as long as a decade.

The mechanism underlying the transition to what is termed hormone refractory disease is unclear. Most theories point to a change in the cancer cells, which normally have receptors that specifically recognize testosterone, much like a key fitting a lock. With time, the "lock" changes such that many "keys" can now fit within the lock and activate or promote cell growth. It also appears that many prostate cancer cells increase the number of receptors or "locks" so they can now be activated by extremely low levels of testosterone. In general these patients have few options and are thus a focus of the Barbara and Maurice Deane Prostate Health Center.

After a full evaluation to stage the extent of the disease accurately, patients are treated with second- and third-line hormonal manipulations. These include the removal of existing or adding new drugs such as anti-androgens (Casodex, Nicandron). In the short term these manipulations may control the rise in PSA and perhaps even decrease PSA. The longevity of such manipulations in our experience is in terms of 6 to 12 months. Other manipulations include the use of Ketoconazol an antifungal agent which will inhibit the production of androgens made from the adrenal glands in combination with Hydrocontine.

Until recently, chemotherapeutic agents were completely ineffective in patients with hormone refractory prostate cancer. Mount Sinai has extensive experience using Taxol and Estramustine for treating such patients. In a recently published study, Dr. Ferrari, our Director of Medical Oncology, found that three-fourths of patients taking weekly Taxol and Estramustine for three days in six-week cycles had a greater than fifty percent reduction in their PSA levels with this treatment. In fact, most have a reduction of up to 75%. While this chemotherapeutic regimen may not yet be considered a gold standard, many patients screened with hormone refractory disease are treated with this regimen.