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Advanced (Metastatic) prostate cancer occurs when a tumor that develops in the prostate gland spreads outside the prostate. The most common sites of prostate cancer spread are to the lymph nodes and bones. This is also called metastatic prostate cancer. Currently, no treatments can cure advanced/metastatic prostate cancer. However, there are effective ways to help slow its spread, prolong life, and control its symptoms, including immunotherapy, hormone therapy, chemotherapy, precision medicine and clinical trials.
What are the treatment options for advanced prostate cancer?
Immunotherapy / Provenge
Immunologic agents are used to stimulate a patient’s own immune system to respond against the cancer. For patients with advanced prostate cancer, Provenge (sipuleucel-T) is an immunotherapy treatment that utilizes the power of the patient’s own immune system to identify and target prostate cancer cells. Each dose is manufactured specifically for each patient. The process of making Provenge involves collecting a patient's immune cells in a procedure called leukapheresis, and growing them in the laboratory in the presence of a protein that stimulates the immune cells to recognize prostate-cancer. This process activates the patient's immune cells to help the immune system better fight the disease. Provenge immunotherapy treatment typically takes one month to be administered, and is given in three intravenous infusions every two weeks. Provenge was approved by the U.S. Food and Drug Administration (FDA) for the treatment of men with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer and is made by Dendreon Corporation. Studies have shown that in patients with metastatic prostate cancer, Provenge has allowed men to live longer with minimal side effects. Provenge is available for patients being treated at UCLA Urology as part of our standard of care regimen. Learn more about Provenge.
Male hormones, specifically testosterone, support the growth of prostate cancer. By reducing the amount of testosterone in the body, the growth and spread of prostate cancer can be slowed. Hormone therapy, also known as androgen ablation or androgen-deprivation therapy, is the primary approach in the treatment of advanced prostate cancer.
The majority of the male hormone testosterone is produced by the testicles, and the surgical removal of the testicles was once a common way to treat advanced prostate cancer. However, because it requires surgery and is irreversible, nearly all men today choose drug therapy instead.
Gonadotropin-releasing hormone (GnRH) analogues (also called LHRH, or luteinizing-hormone releasing hormones) such as leuprolide (Eligard, Lupron, and Viadur), goserelin (Zoladex), and triptorelin (Trelstar) suppress production of testosterone by the testicles, while antiandrogens such as such as bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron) block the effects of testosterone in the body. These two different kinds of drugs are often given together. There are now newer forms of antiandrogens such as Xtandi (MDV-3100, enzalutamide) and drugs such as Zytiga (abiraterone) are able to block testosterone production in not only the testicles, but in other areas of the body such as the adrenal glands and the tumor itself. Abiraterone is now approved for administration for men for men who present with evidence of metastatic prostate cancer, providing an alternative to chemotherapy. Regardless of the specific type of hormone therapy, side effects common to all these drugs include hot flashes, mood swings, loss of sex drive and erectile dysfunction, heart problems, and loss of bone density and muscle mass with long-term use. For men with cancer that has spread to the bone, drugs such as Zometa (zoledronate) and Xgeva (denosumab), help treat osteoporosis and can prevent or delay the skeletal complications associated with the spread of prostate cancer.
Although hormone therapies are effective in the majority of men, they are not curative and most men progress to what is called hormone-refractory or androgen-independent prostate cancer.
Patients who no longer respond to hormone therapy have other treatment options. At one time, chemotherapy was used only to relieve symptoms associated with symptomatic metastatic disease. However, since 2004 it has been known that docetaxel (Taxotere) can prolong the lives of men with prostate cancer that no longer respond to hormone therapy and it is now the standard chemotherapy regimen for patients in this setting. Docetaxel is usually taken with prednisone (a steroid), requires an intravenous infusion every three weeks, and works by preventing cancer cells from dividing and growing. Side effects of docetaxel are similar to most chemotherapy drugs and include nausea, hair loss, and bone marrow suppression (the decline or halt of blood cell formation). Patients may also experience tingling, numbness, or pain in the fingers or toes, and fluid retention.
In 2011, cabazitaxel (Jevtana) was approved as a second line chemotherapy for men with metastatic prostate cancer when they have progressed during, or after, treatment with docetaxel. Like docetaxel, cabazitaxel is used in combination with the steroid prednisone. Studies with cabazitaxel has shown prolonged overall survival (the length of time before death) in men who received cabazitaxel (Jevtana) in combination with prednisone as compared to those who received the chemotherapy drug mitoxantrone in combination with prednisone. Side effects in those treated with cabazitaxel include significant decrease in infection-fighting white blood cells (neutropenia), anemia, low level of platelets in the blood (thrombocytopenia), diarrhea, fatigue, nausea, vomiting, constipation, and weakness.
With advances in genomic sequencing of prostate cancer (examining the biologic make-up of individual prostate cancers), our medical oncologists are better able to guide treatment choices. Our team will often analyze metastatic biopsies or circulating tumor DNA to determine actionable mutations. Based on these findings you may benefit from more tailored treatment. For those tumors with BRCA or DNA repair alterations, we use a more targeted therapy called PARP inhibitors. For tumors with mismatch repair gene mutations, we use immunotherapy—PD1 and PDL1 inhibitors.
Clinical trials are essential for developing new methods of preventing, diagnosing and treating prostate cancer. The UCLA Prostate Cancer Program offers patients access to ground-breaking experimental drugs in its Clinical Trials Program that allows patients to receive tomorrow’s approved drugs today. Prostate Cancer Clinical Trials Open for Enrollment
Many patients who have no other FDA approved treatment options available often consider participating in clinical trials. Clinical trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. Clinical trials are commonly classified into several phases, each having a different purpose. In phase I studies, researchers test an experimental drug in a small group of people to determine a safe dose, or to evaluate its safety and side effects. In phase II studies, the treatment is tried in larger groups of patients or in specific diseases to further evaluate its safety and efficacy. Phase III studies are used to compare the efficacy of the new treatment to an existing approved treatment. Placebos, or “sugar pills,” may be used as the comparison to the investigational treatment in clinical trials for diseases that have no approved treatment. If the drug successfully passes through all 3 phases, it will usually be approved by the FDA for use in the general population.
Many currently approved drugs such as Xtandi, Zytiga, and Provenge were available to UCLA patients participating in clinical trials years earlier than they would have been otherwise had they needed to wait for approved by the FDA.