PROSTATE CANCER: CHEMOTHERAPY

Prostate cancer is the third leading cause of cancer deaths among men in the United States. Over the past 10 years chemotherapy treatments have been shown to improve pain control and survival for patients with advanced prostate cancer, who have progressed despite hormonal therapy. What is chemotherapy? What are some of the chemotherapeutic agents used to fight prostate cancer? The following information should help answer these questions.

What is the prostate?
The prostate, a part of the male reproductive system, is about the same size and shape as a walnut and weighs about an ounce. It is located below the bladder and in front of the rectum, and surrounds the urethra, the tube-like structure that carries urine from the bladder out through thepenis. The main function of the prostate is to produce ejaculatory fluid.

What is prostate cancer?
Prostate cancer is a significant health care problem in the United States due to its high incidence. It is the most common cancer in men affecting over 192,000 American men annually with approximately 27,000 of diagnosed men dying each year. Prostate cancer is different from most cancers in that a large considerable percentage of men, particularly older men with a shorter life expectancy, may have a “silent form” of this cancer—it will not cause symptoms or spread beyond the prostate gland during their lifetime. Sometimes this cancer can be small, slow growing and present limited risk to the patient. Clinically important prostate cancers can be defined as those that threaten the well-being or life span of a man.

What is chemotherapy?
In contrast to surgery and radiation therapy that remove, destroy or damage cancer cells in a specific area, chemotherapy works throughout the body via the bloodstream. Chemotherapy can destroy cancer cells that have metastasized, or spread from the prostate gland to other parts of the body, including bones, lymph nodes or organs like the liver or lungs. Chemotherapy refers to drug treatment that is used to destroy cancer cells. The drugs circulate throughout the body in the bloodstream and can kill any rapidly growing cells, including both cancerous and non-cancerous ones. Chemotherapy drugs are carefully controlled in both dosage and frequency so that cancer cells are destroyed while the risk to healthy cells is minimized. Often, it is not the primary therapy for prostate cancer patients, but may be used when prostate cancer has spread outside of the prostate gland. There are many different types of chemotherapy drugs and combinations used in all kinds of cancers. The specific characteristics of these drug regimens determine the side effect profiles that can range from a mere nuisance to life threatening complications.

What are some of the side effects of chemotherapy?
Common side effects of chemotherapy depend on the type of drug used, dosage and length of treatment. For prostate cancer patients, the most frequently used chemotherapy regimen is docetaxel and prednisone. The most common side effects of this regimen are fatigue, nausea and vomiting, diarrhea, hair loss, taste changes and a decrease in blood cell counts that result in an increased risk of infections. To minimize the side effects, chemotherapy drugs are carefully monitored according to the amount and number of times they are administered by your physician. Supportive medication is also given to further help offset the side effects caused by the drugs. For instance, new drugs to prevent nausea and vomiting can minimize these side effects. Most side effects disappear once chemotherapy is stopped.

How is chemotherapy administered?
Many chemotherapy drugs are administered directly into a vein through an intravenous catheter while others may be taken by mouth. Some of the drugs must be given in the doctor’s office or clinic; others can be administered while the patient is at home. Hospitalization is rarely needed unless side effects occur.

What are some of the new chemotherapy drugs currently being tested?
Over the last 10 years, two chemotherapy regimens have established a clinical benefit in patients with stage IV (metastatic) prostate cancer that has progressed despite testosterone suppression (so-called hormone-refractory or castrate-resistant prostate cancer). Mitoxantrone was the first chemotherapy approved for the treatment of prostate cancer, based upon 2 Phase III trials that demonstrated an improvement in pain control for patients with symptomatic prostate cancer. More recently, two different Phase III clinical trials established a superior regimen to mitoxantrone. In these studies, men with metastatic, advanced hormone-refractory prostate cancer received a treatment regimen with either a chemotherapy called docetaxel or mitoxantrone. In each of these trials, symptom improvement, substantial PSA reduction, and increased overall survival were significantly more likely to occur in the group of men who received docetaxel versus another drug called mitoxantrone. Thus the current standard of care is to use docetaxel chemotherapy with a low dose of a steroid pill treatment of metastatic hormone-refractory (or castrate-resistant) prostate cancer.

Currently there several promising clinical trials to improve upon this chemotherapy. A number of interesting new drugs are being developed to combine with docetaxel. They include bevacizumab (Avastin), ZD5054 (Zibotensan), atrasentan (Xinlay) and OGX-11. In preliminary studies, each of these drugs, when combined with docetaxel, caused substantial PSA declines in more than 50 percent of men as well as symptomatic improvement in men with advanced disease. Each of these drug regimens are now being compared to docetaxel alone in separate phase III clinical trials. All men with metastatic prostate cancer who are considering chemotherapy are encouraged to enter these trials when available.

The encouraging results of docetaxel in advanced prostate cancer have caused the initiation of other studies investigating this regimen in earlier stages of prostate cancer. For example, there are many studies underway adding docetaxel to surgery or radiation therapy for men with stage III (cancer has spread to surrounding tissue or seminal vesicles) or high-risk prostate cancer. Other studies are looking at the addition of docetaxel chemotherapy to hormonal therapy in men who have not progressed on hormonal therapy (so-called hormone-sensitive prostate cancer). Finally, Other studies are evaluating new treatments for prostate cancer before or after chemotherapy. These agents, vary from vaccines which induce immune responses against prostate cancer (Spicuecel) to new drugs that inhibit testosterone (androgen) synthesis (i.e. abirateone) or androgen receptor inhibition (i.e. MDV3100).

For patients whose disease has progressed despite docetaxel chemotherapy, there are currently noFDA approved agents and participation in clinical trials is highly encouraged. Current options include best supportive care, alternative chemotherapeutic regimens, bisphosphonates (bone-strengthening agents), radiation therapy, additional hormonal manipulations, and steroids. One recently completed Phase III study in this setting is Abiraterone combined with prednisone compared to prednisone plus placebo. Other ongoing Phase III trials in this setting include MVD-3100 vs. placebo and the multitargeted tyrosine kinase inhibitor sunitinib (sutent) and prednisone vs. prednisone and placebo.

Frequently asked questions:

What are the advantages and disadvantages of chemotherapy? How do I know if it’s right for me?
Chemotherapy can significantly improve survival and relieve symptoms of advanced prostate cancer. Markers of response, including declines in serum PSA levels may aid in determining the benefit obtained by chemotherapy. In general, the lower the decline in PSA the greater the survival seen in patients. However, because chemotherapy is an aggressive treatment with side effects, it is important to discuss your treatment options with your doctor.

Can I take other medicines while I am getting chemotherapy?
Some medicines may interfere with the effects of your chemotherapy drugs. To ensure that your treatment is the most effective that it can be, tell your doctor about any and all prescription and non-prescription medicines you are taking. Your doctor will tell you if you should stop taking any of these medicines before you start chemotherapy. After your treatments begin, check with your doctor before taking any new medicines or stopping the ones you already take.

Can I continue with my normal activities while I am getting chemotherapy?
Whether you can continue work, school or other activities depends on your treatment and how it affects you. Hospitalization is not needed for the treatments and most people are able to continue their activities during treatment. You might be able to schedule your treatments late in the day or before the weekend to minimize their interference with your activities.

Where can I get more information?

Know Your Stats About Prostate Cancer Treatment Options: Chemotherapy