The lancet oncology
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The lancet oncology · Oct 2009
Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target.
Activation of the androgen receptor is crucial for prostate cancer growth at all points of the illness. Current therapies targeting the androgen receptor, including androgen-depletion approaches and anti-androgens, do not completely inhibit the receptor activity. Prostate cancer cells develop resistance to castration by acquiring changes that include androgen-receptor overexpression and overexpression of enzymes involved in androgen biosynthesis, which result in reactivation of the receptor. ⋯ Notably, promising activity has been shown in early phase trials by MDV3100, a new anti-androgen designed for activity in prostate cancer model systems with overexpressed androgen receptor, and by abiraterone acetate, a CYP17A inhibitor that blocks steroid biosynthesis in the adrenal gland and possibly within the tumour. Both agents are undergoing phase 3 testing. Here, we review the basic science and clinical development of these and other agents.
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The lancet oncology · Sep 2009
Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials.
Bisphosphonates might modulate the development of symptomatic bone metastases in men with prostate cancer. The Medical Research Council (MRC) PR05 and PR04 randomised controlled trials assessed the use of sodium clodronate, an oral, first-generation bisphosphonate. We report the final analyses of long-term survival data with additional follow-up in both trials. ⋯ UK MRC; and an education grant and free drug from Roche Products Ltd.