Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

• Published in: The New England journal of medicine Vol. 367; no. 13; pp. 1187 - 1197
• Main Authors: Scher, Howard I, Fizazi, Karim, Saad, Fred, Taplin, Mary-Ellen, Sternberg, Cora N, Miller, Kurt, de Wit, Ronald, Mulders, Peter, Chi, Kim N, Shore, Neal D, Armstrong, Andrew J, Flaig, Thomas W, Fléchon, Aude, Mainwaring, Paul, Fleming, Mark, Hainsworth, John D, Hirmand, Mohammad, Selby, Bryan, Seely, Lynn, de Bono, Johann S
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 27.09.2012
• Subjects: Aged; Androgen Receptor Antagonists - adverse effects; Androgen Receptor Antagonists - therapeutic use; Androgen receptors; Androgens; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Castration; Chemotherapy; Clinical trials; Diarrhea; Disease-Free Survival; Docetaxel; Double-Blind Method; Fatigue; General aspects; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; Male; Male genital diseases; Medical sciences; Men; Metastases; Middle Aged; Multivariate Analysis; Neoplasm Metastasis - drug therapy; Nephrology. Urinary tract diseases; Orchiectomy; Pain; Phenylthiohydantoin - adverse effects; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - surgery; Seizures; Seizures - chemically induced; Signal transduction; Signal Transduction - drug effects; Survival; Taxoids - therapeutic use; Testosterone; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Medicine; Chemotherapy; Urinary system disease; Treatment; Prostate disease; Malignant tumor; Male genital diseases; Prostate cancer; Survival; Cancer
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1207506

In a study involving nearly 1200 men with metastatic prostate cancer who had progressive disease after chemotherapy, enzalutamide, a novel androgen-receptor blocker, extended the median survival by nearly 5 months, as compared with placebo (18 months vs. 13 months). Prostate cancer is an androgen-dependent disease that initially responds but later becomes resistant to established therapies that reduce circulating testosterone levels or inhibit androgen binding to the androgen receptor. 1 – 4 Reactivation of the disease despite castrate levels of testosterone represents a transition to the lethal phenotype of castration-resistant prostate cancer. 5 , 6 This state was previously called androgen-independent or hormone-refractory prostate cancer but is now recognized to be driven by androgen-receptor signaling, in part due to overexpression of the androgen receptor itself. 7 , 8 In preclinical models of prostate cancer, androgen-receptor overexpression shortens the period of tumor latency and confers resistance to . . .