New treatments for castration-resistant prostate cancer

This review examines the current and future treatment options for metastatic castration-resistant prostate cancer.

The initial treatments offered to most patients with prostate cancer include radiation therapy or prostatectomy (surgical removal of the prostate). These treatments effectively reduce the size of and remove the tumor, leading to 5-year survival rates of close to 100%. Some patients, however, still experience recurrence and metastasis (spread) of the disease. In additional patients, around 10% to 20%, the cancer has already metastasized at the time of diagnosis.

Patients with advanced cases receive androgen deprivation therapy, which decreases the levels of or blocks the body using testosterone, the male hormone needed for prostate tumor growth. Androgen deprivation therapy can decrease tumor growth, prostate-specific antigen (a protein elevated in prostate cancer) levels, and symptoms of the disease. In many of these patients, however, the cancer becomes castration resistant, meaning it no longer responds to androgen deprivation therapy.

90% of patients with castration-resistant prostate cancer will experience a rise in PSA levels, an increase in symptoms, and pain from bone metastasis, which decreases the quality of life and is a main cause of mortality. The current review examines treatments for castration-resistant prostate cancer patients.

The primary treatment often used in castration-resistant patients is docetaxel (Taxotere), a type of chemotherapy known as a taxane. Docetaxel limits tumor growth by interfering with cell division, which is very rapid in cancer cells.  It is generally administered with a corticosteroid, such as prednisone (Deltasone), which decreases inflammation. When compared to other chemotherapy/steroid combinations, treatment with docetaxel and prednisone increased the overall survival time by 2.9 months, led to a 50% decrease in PSA levels, and improved pain and quality of life.

 Docetaxel, however, has led to toxicities in 26% of patients, and many men eventually become resistant to the treatment. For patients who cannot tolerate docetaxel, mitoxantrone (Novantrone) is another taxane that can be tried. Other therapies for castration-resistant prostate cancer include immunotherapies, which encourage the immune system to attack cancer cells as it would bacteria or a virus. Sipuleucel-T (Provenge; an immunotherapeutic drug) has shown a 4.1 month improvement in overall survival time compared to a placebo (a substance with no effect on the body that can be used as a control).

Newer treatments for castration-resistant prostate cancer are targeted therapies, which work by blocking signaling pathways, the means by which cells and body tissue communicate to promote cancer growth. Blocking signaling enzymes called tyrosine kinases  can slow cell growth and increase cell death. Tyrosine kinase inhibitors, such as dasatinib (Sprycel), can be combined with docetaxel and have been found to block bone metastasis in mice. A current trial is examining the dasatinib/docetaxel combination in humans, and has shown a partial response (such as tumor shrinkage) in 60% of patients and reduced PSA levels in 57%. 61% of these patients were able to discontinue use of docetaxel and remain progression free for up to a year. Trials examining the overall survival associated with this treatment combination are underway.

Custirsen is another treatment targeting the signaling pathways, blocking the protein clusterin and decreasing the rate of cell growth.  A recent trial has shown that combining custirsen with docetaxel and prednisone increased overall survival by 7 months compared to docetaxel and prednisone alone, and 58% of patients saw a decrease of 50% or more in PSA levels.

This study concluded that targeted treatments under development, such as dasatinib and custirsen, are proving to be safe and effective therapies for metastatic castration-resistant prostate cancer.

Discuss the appropriate treatment options for your situation with your physician.