title: Effect of abiraterone acetate plus prednisone on the QT interval in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  Abiraterone is the active metabolite of the pro-drug abiraterone acetate (AA) and a selective inhibitor of CYP17, a key enzyme in testosterone synthesis, and improves overall survival in postdocetaxel metastatic castration-resistant prostate cancer (mCRPC). This open-label, single-arm phase 1b study was conducted to assess the effect of AA and abiraterone on the QT interval.
  
  
  METHODS
  The study was conducted in 33 patients with mCRPC. Patients received AA 1,000 mg orally once daily + prednisone 5 mg orally twice daily. Electrocardiograms (ECGs) were collected in triplicate using 12-lead Holter monitoring. Baseline ECGs were obtained on Cycle 1 Day-1. Serial ECG recordings and time-matched pharmacokinetic (PK) blood samples were collected over 24 h on Cycle 1 Day 1 and Cycle 2 Day 1. Serial PK blood samples were also collected over 24 h on Cycle 1 Day 8.
  
  
  RESULTS
  After AA administration, the upper bound of the 2-sided 90 % confidence interval (CI) for the mean baseline-adjusted QTcF change was <10 ms; no patients discontinued due to QTc prolongation or adverse events. No apparent relationship between change in QTcF and abiraterone plasma concentrations was observed [estimated slope (90 % CI): 0.0031 (-0.0040, 0.0102)].
  
  
  CONCLUSIONS
  There is no significant effect of AA plus prednisone on the QT/QTc interval in patients with mCRPC.
authors: South Texas Accelerated Research Therapeutics (START), Center for Cancer Care, San Antonio, TX 78229, USA. atolcher@start.stoh.com
authors: A W
authors: AW
authors: Tolcher
authors: K N
authors: KN
authors: Chi
authors: N D
authors: ND
authors: Shore
authors: R
authors: R
authors: Pili
authors: A
authors: A
authors: Molina
authors: M
authors: M
authors: Acharya
authors: T
authors: T
authors: Kheoh
authors: J J
authors: JJ
authors: Jiao
authors: M
authors: M
authors: Gonzalez
authors: A
authors: A
authors: Trinh
authors: C
authors: C
authors: Pankras
authors: N
authors: N
authors: Tran
mesh_terms: D000069501:Abiraterone Acetate; D000728:Androgens / Q000378:metabolism; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors
chemical_list: D000728:Androgens; D000730:Androstadienes; D013254:Steroid 17-alpha-Hydroxylase; D000069501:Abiraterone Acetate; D011241:Prednisone