title: Evaluation of the relationship between cetuximab therapy and corrected QT interval changes in patients with advanced malignancies from solid tumors.
abstract: OBJECTIVE
  Greater scrutiny is being placed on developing a full understanding of potential cardiotoxicity of therapeutic agents, especially on the potential to prolong the QTc interval which can lead to arrhythmias such as torsade de pointes and sudden death. This trial was designed to specifically evaluate the effect, if any, of cetuximab on the QTc interval in patients with advanced solid tumors.
  
  
  METHODS
  Cetuximab was administered as an initial dose of 400 mg/m(2) on day 1 (week 1) followed by a maintenance dose of 250 mg/m(2) weekly thereafter. ECG monitoring was performed at screening, baseline (week 1 preceding dosing), and during week 1 to 5 of treatment. Cetuximab concentration-to-QTc relationship was evaluated based on cetuximab serum samples obtained at the time of each ECG measurement to allow for accurate correlation between any observed QT/QTc changes and cetuximab serum concentration.
  
  
  RESULTS
  At the recommended dose (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), cetuximab had no clinically meaningful effect on QTc interval, PR or QRS intervals, or heart rate and there was no apparent concentration-dependent effect of cetuximab on any of these electrocardiogram parameters. Safety observations in patients treated with cetuximab in this study were consistent with the agent's known safety profile.
  
  
  CONCLUSIONS
  These results suggest that cetuximab can be safely administered as a single agent without risk of effect on QTc interval.
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, NW, Washington, DC 20007, USA. John.Deeken@gunet.georgetown.edu
authors.forename: J F
authors.initials: JF
authors.lastname: Deeken
authors.forename: B
authors.initials: B
authors.lastname: Shimkus
authors.forename: A
authors.initials: A
authors.lastname: Liem
authors.forename: D
authors.initials: D
authors.lastname: Hill
authors.forename: J
authors.initials: J
authors.lastname: Gurtler
authors.forename: E
authors.initials: E
authors.lastname: Berghorn
authors.forename: L
authors.initials: L
authors.lastname: Townes
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: O
authors.initials: O
authors.lastname: Trifan
authors.forename: S
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000068818:Cetuximab; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab