title: Orteronel for the treatment of prostate cancer.
abstract: Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer. Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Preclinical studies demonstrate that orteronel treatment suppresses androgen levels and causes shrinkage of androgen-dependent organs, such as the prostate gland. Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone. Treatment with single-agent orteronel has been well tolerated with fatigue as the most common adverse event, while febrile neutropenia was the dose-limiting toxicity in a combination study of orteronel with docetaxel. Recently, the ELM-PC5 Phase III clinical trial in patients with advanced-stage prostate cancer who had received prior docetaxel was unblinded as the overall survival primary end point was not achieved. However, additional Phase III orteronel trials are ongoing in men with earlier stages of prostate cancer.
authors.affiliation: Division of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Van Hook
authors.forename: Ted
authors.initials: T
authors.lastname: Huang
authors.forename: Joshi J
authors.initials: JJ
authors.lastname: Alumkal
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000096:biosynthesis; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D007093:Imidazoles; D009281:Naphthalenes; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D017430:Prostate-Specific Antigen; C571806:orteronel