Advanced Prostate Cancer: New Drug Therapies
With no cure currently available for advanced prostate cancer, the goal is to turn castration-resistant prostate cancer (when the effect of testosterone suppression wanes and the disease progresses) into a chronic but manageable condition.
The use of as many therapies as possible, either in sequence or in various combinations, can extend survival and also improve the quality of life for patients.
Here is a look at therapies currently available for men with advanced prostate cancer.
When men are asymptomatic and before trying chemotherapy, they can try Provenge (sipuleucel-T), the first vaccine therapy approved by the U.S. Food and Drug Administration in the armamentarium for advanced cancer.
In a large Phase III clinical trial (called IMPACT), Provenge was found to extend the lives of patients with advanced, metastatic, castration-resistant prostate cancer by an average of four months when compared with patients given a placebo.
Provenge is a novel option—a therapeutic vaccine given to men with advanced prostate cancer to get their own immune systems to attack and eliminate the cancer. The FDA approved Provenge in 2010. Provenge is currently indicated for patients who have failed hormone therapies and have metastatic disease. In addition, they have to exhibit no symptoms (or very minimal symptoms) from their prostate cancer.
Although the FDA label doesn’t clearly state that the patients have to be chemotherapy-naïve (an oncology term meaning that the person never had chemotherapy treatment), oncologists recommend that they get Provenge before chemotherapy.
Provenge is made from a patient’s own immune cells and is used to stimulate his own immune system against their cancer. The process takes several steps: three days before the infusion, some of the patient’s blood is withdrawn at a blood collection center.
The blood is then run through a machine in a process known as “leukapheresis” (white blood cell extraction). During the process, some of the man’s immune cells are collected and then exposed to a special protein intended to stimulate and direct them against prostate cancer.
Following this exposure, the activated immune cells are returned to the doctor’s office and are then reinfused back into the man’s body to treat the prostate cancer.
Provenge is given only to the patient from whom the cells were obtained. It is administered intravenously in a three-dose schedule at approximately two-week intervals.
The FDA approved Jevtana (cabazitaxel)in 2010 based on the results of the TROPIC trial, which reported that the drug increased survival by 30 percent in men with metastatic cancer unresponsive to the chemotherapy drug Taxotere.
Jevtana is thought to work by interfering with the microtubules in the tumor, stopping the cancer cells from growing and multiplying.
Jevtana does have side effects, including febrile neutropenia, which is a high fever caused by the drug’s ability to reduce the number of circulating white blood cells, or neutrophils, which protect the body from infection. The fewer neutrophils in the body, the more vulnerable it is to infection.
Diarrhea can be another troublesome side effect with Jevtana. Fortunately, significant neuropathy almost never occurs.
Zytiga (abiraterone)is an oral drug that blocks CYP17, a key driver of testosterone production in the adrenal gland and in the prostate tumor itself.
Zytiga caused the vast majority of patients in the Phase III clinical trial to have significant reductions in their prostate-specific antigen (PSA) levels. What this shows is that metastatic castration-resistant prostate cancer remains driven by testosterone.
Most patients who use Zytiga also have significant shrinkage of tumors, and for those with bone pain because of metastases, many will also experience improvement in pain levels.
Xtandi (enzalutamide) is an oral drug specifically designed to overcome some of the limitations of the other antiandrogens, including Casodex (bicalutamide), Nilandron (nilutamide), and Eulexin (flutamide).
While all three block the testosterone receptor, they are fairly weak and only work in 60 percent to 75 percent of patients. Over time, those drugs can also exacerbate or promote cancer growth (that is, they can act as stimulants instead of blockers).
Xtandi is the strongest inhibitor of testosterone receptors available. The drug blocks testosterone receptors at three separate points, preventing testosterone from traveling into the nucleus of a cell and stimulating the genes that cause prostate cancer growth. Xtandi also prevents the testosterone receptor from binding to DNA.