MDV3100 is an androgen receptor antagonist drug developed with promise for castration-resistant prostate cancer, where it is in Phase 3 clinical trials and for breast cancer. MDV3100 has approximately fivefold higher binding affinity for the androgen receptor (AR) than Casodex and it does not promote translocation of AR to the nucleus like Casodex. In addition, it prevents binding of AR to DNA and AR to coactivator proteins.
Median time to radiographic progression in phase II studies was 56 weeks for chemo-naive patients and 25 weeks for patients previously treated with chemotherapy. A phase III trial AFFIRM (NCT00974311), in men with metastatic castration-resistant prostate cancer (CRPC) who had progressed after treatment with docetaxel-based chemotherapy, was was stopped in November 2011 after a planned interim analysis showed a 37% reduction in the risk for death with MDV3100 over placebo (median, 18.4 vs 13.6 months; hazard ratio [HR], 0.631; P < .0001). Based on this, the drug was approved as Xtandi for patients who failed docetaxel.
Another phase III trial, PREVAIL(NCT01212991) is in patients who are chemo naive. There is also a phase II trial began in March 2011 comparing MDV3100 with Casodex in patients patients who have progressed while on LHRH analogue therapy (e,g., leuprorelin) or surgical castration.
Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (May 2009). “Development of a second-generation antiandrogen for treatment of advanced prostate cancer”. Science 324 (5928): 787–90.
Howard I Scher MD,Tomasz M Beer MD,Celestia S Higano MD,Aseem Anand MA,Mary-Ellen Taplin MD,Eleni Efstathiou MD,Dana Rathkopf MD,Julia Shelkey BS,Evan Y Yu MD,Joshi Alumkal MD,David Hung MD,Mohammad Hirmand MD,Lynn Seely MD,Michael J Morris MD,Daniel C Danila MD,John Humm PhD,Steve Larson MD,Martin Fleisher PhD,Charles L Sawyers MD,the Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study The Lancet – 24 April 2010 ( Vol. 375, Issue 9724, Pages 1437-1446 )
William L Dahut,Ravi A Mada Revisiting the ultimate target of treatment for prostate cancer The Lancet – 24 April 2010 ( Vol. 375, Issue 9724, Pages 1409-1410 )
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