Drugs in Clinical Development for Prostate Cancer
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Pharm Med 2011; 25 (6): 387-404 1178-2595/11/0006-0387/$49.95/0
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Drugs in Clinical Development for Prostate Cancer Summary and Table
Prostate cancer is the second most commonly diagnosed malignancy in men. In 2008, around 910 000 men worldwide were estimated to be newly diagnosed with prostate cancer. The incidence of the disease is expected to almost double by 2030. However, mortality from prostate cancer is declining in some developed countries, partly because of early detection and improved treatment. There are several treatment options available for patients with prostate cancer, including radical prostatectomy, radiotherapy, hormonal therapy and chemotherapy, depending on the stage of disease. In patients with localized prostate cancer and/or a short life expectancy, active surveillance may be suitable; otherwise, radical prostatectomy or radiotherapy are potentially curative treatment options. For patients with locally advanced or metastatic prostate cancer, hormonal therapy or androgen deprivation therapy (ADT) is a cornerstone of disease management. ADT decreases circulating testosterone levels and prevents prostate cancer cell growth. Early treatment with hormone therapy has been shown to improve survival; consequently, ADT is increasingly being used to treat earlier stages of disease, including high-risk localized prostate cancer. ADT for prostate cancer using surgical castration or estrogen therapy was first developed in the 1940s, after it was discovered that prostate cancer growth is dependent on testosterone. In the 1970s, physicians often chose to use surgical castration because of cardiovascular risks associated with estrogen therapy, although estrogen therapy was preferred by patients. Of the currently available agents for chemical castration (luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, antiandrogens and estrogen), LHRH agonists have become the mainstay of treatment for advanced and metastatic prostate cancer. LHRH agonists were first introduced in the 1980s, and were initially of limited clinical use
because of short half-lives. Manipulation of the LHRH amino acid sequence led to development of analogues with longer halflives and increased potency. LHRH agonists are administered as depot injections that last for up to 1 year, and a once-yearly subcutaneous implant is also available. Patients with metastatic prostate cancer eventually develop disease progression despite chemical castration, defined as castration-resistant prostate cancer. Chemotherapy with docetaxel has become the standard of care for these patients, but in the past few years there have been important developments in targeted therapy and immunotherapy. Various classes of agents are in clinical development for castration-resistant prostate cancer, including endothelin receptor antagonists, RANK-L inhibitors, antiangiogenic agents, androgen receptor antagonists and tyrosine kinase inhibitors. In the field of immunotherapy, the prostate cancer vaccin
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