title: Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs.
abstract: BACKGROUND
  Cardiac sequelae from oncologic drugs are important in early cancer drug development. Prolongation of the corrected QT interval (QTc) by noncardiac drugs is the most common cause of drug development delays, nonapprovals and postmarketing withdrawals by the US Food and Drug Administration.
  
  
  METHODS
  We analyzed 8518 electrocardiograms (ECGs) in 525 consecutive cancer patients enrolled in 22 industry-sponsored phase I clinical trials, starting 1 January 2006.
  
  
  RESULTS
  Seventy-four patients [14%, 95% confidence interval (CI) 11% to 17%] with normal QTc at baseline had QTc intervals above upper limit of normal after treatment initiation; 33 (6%, 95% CI 4% to 9%) had prolonged QTc intervals at baseline, and only one (3%, 95% CI 0% to 16%) worsened after dosing. Seven of 33 patients (21%, 95% CI 9% to 39%) with prolonged baseline QTc had normalization of QTc intervals after dosing. All QTc prolongations were clinically insignificant; study drugs were continued uneventfully. Two of 525 patients (0.4%, 95% CI 0% to 1%) experienced cardiac serious adverse events (myocardial infarction possibly related to drug and unstable atrial flutter related to metastatic disease). Both cardiac events were detected by clinical assessment, not surveillance ECGs.
  
  
  CONCLUSIONS
  Frequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.
authors: Departments of Investigational Cancer Therapeutics. Electronic address: anaing@mdanderson.org.
authors: A
authors: A
authors: Naing
authors: Departments of Investigational Cancer Therapeutics.
authors: H
authors: H
authors: Veasey-Rodrigues
authors: Departments of Investigational Cancer Therapeutics.
authors: D S
authors: DS
authors: Hong
authors: Departments of Investigational Cancer Therapeutics.
authors: S
authors: S
authors: Fu
authors: Departments of Investigational Cancer Therapeutics.
authors: G S
authors: GS
authors: Falchook
authors: Departments of Investigational Cancer Therapeutics.
authors: J J
authors: JJ
authors: Wheler
authors: Departments of Investigational Cancer Therapeutics.
authors: A M
authors: AM
authors: Tsimberidou
authors: Departments of Biostatistics.
authors: S
authors: S
authors: Wen
authors: Departments of Investigational Cancer Therapeutics.
authors: S N
authors: SN
authors: Fessahaye
authors: Departments of Investigational Cancer Therapeutics.
authors: E C
authors: EC
authors: Golden
authors: Departments of Investigational Cancer Therapeutics.
authors: J
authors: J
authors: Aaron
authors: Departments of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors: M S
authors: MS
authors: Ewer
authors: Departments of Investigational Cancer Therapeutics.
authors: R
authors: R
authors: Kurzrock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents