title: Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer.
abstract: OBJECTIVE
  Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study.
  
  
  METHODS
  In ARMOR1, 49 patients received increasing doses (650-2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700-3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed.
  
  
  RESULTS
  In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events.
  
  
  CONCLUSIONS
  The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition.
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Bruce
authors.initials: B
authors.lastname: Montgomery
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, James Buchanan Brady Urological Institute, Baltimore, Maryland.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.affiliation: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Rettig
authors.affiliation: San Bernadino Urological Associates, San Bernadino, California.
authors.forename: Franklin
authors.initials: F
authors.lastname: Chu
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.affiliation: Institute for Translational Oncology Research, Greenville, South Carolina.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Stephenson
authors.affiliation: Comprehensive Cancer Centers of Nevada and U.S. Oncology Research, Las Vegas, Nevada.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Lynn Cancer Institute, Boca Raton, Florida.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Koletsky
authors.affiliation: Urology Cancer Center and GU Research Network, Omaha, Nebraska.
authors.forename: Luke T
authors.initials: LT
authors.lastname: Nordquist
authors.affiliation: Greenville Hospital System and University Medical Center, Greenville, South Carolina.
authors.forename: William J
authors.initials: WJ
authors.lastname: Edenfield
authors.affiliation: Tokai Pharmaceuticals, Cambridge, Massachusetts.
authors.forename: Khalid
authors.initials: K
authors.lastname: Mamlouk
authors.affiliation: Tokai Pharmaceuticals, Cambridge, Massachusetts.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Ferrante
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts. Mary_Taplin@dfci.harvard.edu.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D019233:Retreatment; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D001562:Benzimidazoles; D011944:Receptors, Androgen; C500627:3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene