Prostate Cancer: Systemic Therapies

Pictured: Michael Morris Michael Morris and other medical oncologists at Memorial Sloan Kettering lead clinical trials of new drugs for the treatment of metastatic prostate cancer.

Men with metastatic prostate cancer — cancers that have spread to the lymph nodes or other parts of the body — have more treatment options than ever before. Better understanding of the biology of prostate cancer has led to the recent development of several new medications that are helping men to survive longer and enjoy a good quality of life. This is true both in men who have metastatic disease at the time of their initial diagnosis and in those who develop metastatic prostate cancer after undergoing radical prostatectomy and/or radiation therapy. Since 2010, six different treatments have been shown to prolong the lives of men with metastatic disease, and four of these have already been approved by the US Food and Drug Administration. Many other systemic therapies are in the late stages of development.

Pictured: Howard Scher
Video

Dr. Howard Scher talks about new hormone treatments, chemotherapy drugs, and other medications for men with advanced prostate cancer.

(06:00)

Memorial Sloan Kettering Cancer Center has been a leader in the effort to develop and increase access to new treatments for prostate cancer. Our scientists have pioneered basic research that underlies some of the most promising drugs currently being tested. Our clinical investigators have also led the way in translating such discoveries into clinical practice. Memorial Sloan Kettering is the coordinating center of the Prostate Cancer Clinical Trials Consortium (PCCTC), a national group to improve patients’ access to new therapies.

Memorial Sloan Kettering's robust research program means that we are able to offer patients access to clinical trials of new treatments, sometimes years before they become widely available. Visit our clinical trials to learn about studies that are currently enrolling new patients.

About Systemic Therapies

Drugs used to manage metastatic prostate cancer are called systemic therapies because they circulate throughout the body to attack cancer cells wherever they may be. Systemic therapies include hormone therapy, chemotherapy, biologic therapies, targeted approaches, and treatments specifically designed to attack prostate cancers that have spread to the bone. These bone targeting agents may be given alone or in combination with other treatments to slow the progression of your disease and prevent osteoporosis (bone loss) that can lead to bone fractures.

Medical oncologists at Memorial Sloan Kettering are experts at determining which treatment or combination of treatments will be most effective for you, considering the specific features of your disease.

Hormone Therapy

The male sex hormone testosterone (also called an androgen) is known to stimulate the growth of prostate cancer cells. Hormone therapy (also known as androgen-deprivation therapy) includes a variety of medications that inhibit this effect by decreasing the production of testosterone or blocking the binding of testosterone to the cancer cells. Hormone therapy can shrink and slow the growth of prostate tumors, even after the cancer has spread to distant sites in the body.

Hormone therapy may be used in the following situations:

  • For some patients with locally advanced disease that has not spread to other parts of the body. This group includes patients with cancers that have extended through the capsule of the prostate or have invaded the seminal vesicles. It also includes those with high Gleason scores or high prostate-specific antigen (PSA) levels who are undergoing radiation therapy.
  • For some patients who have a rising PSA after surgery or radiation therapy.
  • For almost all patients who have been diagnosed with metastatic disease.

Hormone therapy can effectively shrink and control the spread of prostate cancer in many men. After a period of months or years, however, many prostate tumors become resistant to “first-line” hormone therapies. These therapies are designed to reduce a man’s testosterone to “castrate levels,” in other words, to levels that are similar to what is achieved with the removal of the testicles. Men who no longer respond to first-line hormone therapy are therefore said to have “castration-resistant” prostate cancer.

To delay the onset of castration resistance, first-line hormone therapy may be given intermittently — long enough to reduce PSA levels and control cancer growth, then intentionally stopped for a period of time. This strategy can reduce the side effects associated with hormone therapy, which can include hot flashes and erectile dysfunction. Hormone therapy is then restarted if and when the cancer starts to regrow.

The most significant advances in prostate cancer therapies in recent years have been for patients with castration-resistant prostate cancer.

Medical oncologists at Memorial Sloan Kettering led a large-scale, international clinical trial of a new, highly potent hormone therapy called abiraterone acetate (Zytiga™), which recently received FDA approval. Abiraterone acetate blocks a key enzyme involved in testosterone production, lowering the level of testosterone in the tumor and in the blood stream. The drug has been shown to prolong survival in men with cancers that have progressed despite treatment with other hormone therapies and with chemotherapy.(1)

Doctors at Memorial Sloan Kettering are also developing several new drugs that directly block signaling by the androgen receptor, which can continue to stimulate the growth of prostate cancers when the testosterone level is in the castrate range. One of these investigational drugs, called MDV3100, was discovered by a Memorial Sloan Kettering scientist. MDV3100 specifically binds to androgen receptors in cancer cells, blocking the ability of the receptor to drive cancer growth. In a recently reported international clinical trial — also led by Memorial Sloan Kettering medical oncologists — MDV3100 was shown to prolong survival in men with prostate cancers that have progressed after treatment with hormones and chemotherapy.

Research has shown that these drugs improve survival in men with metastatic prostate cancers who do not respond to other treatments.

Chemotherapy

Pictured: Howard Scher
Video

Medical expert Howard Scher describes new medications for the treatment of advanced or recurrent prostate cancer.

(19:00)

Chemotherapy is medication that is given intravenously or by mouth to kill cancer cells. Chemotherapy is an important therapeutic option for men with prostate cancer that has metastasized after hormone therapy, and has been shown to prolong survival and reduce pain from bone metastases.

Docetaxel (Taxotere®), which damages the structure of prostate cancer cells, is considered the standard of care in chemotherapy for men with prostate cancer that is resistant to hormone therapy.

Recently, the FDA approved another chemotherapy drug, cabazitaxel (Jevtana®), for the treatment of metastatic prostate cancers that have progressed in patients taking docetaxzel. Cabazitaxel inhibits the growth of cancer cells.

Immunotherapy (Biologic Approaches)

Immunotherapy, including therapeutic vaccines and other biologic approaches, harnesses the immune system to selectively target cancer cells.

The first ever FDA-approved immunotherapy for metastatic cancer is now available for men with advanced prostate cancer. This new product called sipuleucel-T (Provenge®), is made by harvesting a patient's immune cells, engineering them to fight prostate cancer cells, and reinfusing them into the patient. Provenge has been shown to extend survival in men with metastatic prostate cancer.

Another immunotherapy called ipilimumab (Yervoy®) is currently in phase III clinical trials for the treatment of advanced prostate cancer. This drug was first discovered by a Memorial Sloan Kettering scientist.

Memorial Sloan Kettering physicians and scientists continue to work to develop new immunotherapies to help improve survival for men with metastatic prostate cancer.

Bone-Targeting Treatments

Metastatic prostate cancer commonly spreads to the bones, where it can cause bone pain and fractures. These symptoms can also arise during hormone therapy, when your levels of testosterone are very low. Bone-targeting treatments can reduce the bone loss that may result from hormone therapy, reduce the spread of cancer in the bone, and alleviate pain and minimize other complications of bone metastases.

Two medications are now available to help prevent bone pain and fractures in men with metastatic prostate cancer. These medications work by reducing the ability of tumor cells to thrive in bone. Zoledronic acid (Zometa®), a bisphosphonate, is the current standard of care for men with metastatic prostate cancer. Denosumab (Xgeva®), a new medication that blocks a molecule involved in the formation of bone abnormalities caused by prostate cancer, has recently been approved by the FDA for preventing bone complications related to metastatic disease.

Doctors at Memorial Sloan Kettering are also leading a clinical trial that is testing a drug called Alpharadin to reduce pain caused by bone metastases in men who do not respond to hormone therapy or chemotherapy. Alpharadin contains a radioactive element that specifically targets bone metastases. The radiation that the drug gives out travels only a very short distance in the body, and therefore acts mainly on the areas of the bones that require treatment. Our clinical trial is testing a combination treatment that includes both Alpharadin and the chemotherapy drug Docetaxel.