Chemotherapy
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Introduction

In the last decade, the role of chemotherapy has evolved significantly. The first approved chemotherapy agents, mitoxantrone (Mitoxantrone) and estramustine (Emcyt), were utilized for prostate cancer patients to help control pain and to relieve symptoms associated with their metastatic disease. Because of the drugs’ inherent side effects, doctors were reluctant to prescribe chemotherapy unless patients were experiencing significant problems from the cancer.

Two clinical trials demonstrated an improvement in overall survival with docetaxel (Taxotere®) leading to approval by the FDA in 2004. These trials reported an average survival advantage of only 2.5 months. Many logically ask, “With such a small survival advantage why should I bother?” First, the survival advantage is probably larger than what was reported because men who were not in the docetaxel arm were allowed to cross over and receive docetaxel when their cancer progressed.  So, in a sense, the trial was a study of men who got immediate docetaxel compared to men who got delayed docetaxel.

At the 2010 PCRI Conference, Dr. Vogelzang addressed this issue of survival in a different way. He pointed out that despite the chemo side-effects, quality of life was better. He also pointed out that there is a smaller group of men who benefit with dramatically longer survival. For example, at the same conference, Dr. Scholz pointed out that a 30% PSA decline within 3 months powerfully predicts for dramatically improved survival. The patients whose PSA dropped to less than 4.0 had a huge survival advantage of about 20 months.

When single-agent Taxotere fails, PSA responses have been observed by simply adding other agents including: Avastin (bevacizumab), Xeloda (Capecitabine), thalidomide to Taxotere. Also, the combination of carboplatin, paclitaxel, and estramustine has provided encouraging response rate (40%). In some cases, the response has been very durable, lasting over 12 months.

In 2010, cabazitaxel (Jevtana®) was approved for treatment after docetaxel failure based on an additional survival advantage. Cabazitaxel is a chemotherapy that is similar to but distinct from docetaxel. It is chemically modified and in various model systems has been shown to be active in killing cancer cells even when resistance has developed to other chemotherapy agents.

 

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