title: Challenges of characterizing proarrhythmic risk due to QTc prolongation induced by nonadjuvant anticancer agents.
abstract: BACKGROUND
  Drug-induced QTc prolongation is becoming increasingly important in oncology since novel therapies result in prolonged survival of cancer patients already predisposed to cardiotoxicity.
  
  
  METHODS
  We review the challenges of implementing the ICH E14 guidance in oncology and propose an integrated approach to QTc risk assessment of nonadjuvant anticancer agents (NAAs), with quantitative outcome criteria.
  
  
  RESULTS
  We recommend informed use of non-clinical cardiac safety pharmacology results, some degree of robust ECG assessments in early phase studies, a dedicated QTc study in cancer patients conducted at the appropriate time pre-, peri-, or post-approval (with the design and timing agreed upon with regulatory agencies), and ECG monitoring in late-phase studies commensurate with the outcome of previous QTc studies.
  
  
  CONCLUSIONS
  The proposed approach would facilitate risk-benefit assessment for NAAs during clinical development and regulatory review, and enable adequate labeling for safe and effective postmarketing use in cancer patients.
authors.affiliation: Johnson & Johnson PRD, Welsh & McKean Roads, Spring House, PA 19477-0776, USA. nsarapa@prdus.jnj.com
authors.forename: Nenad
authors.initials: N
authors.lastname: Sarapa
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Britto
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D017277:Drug Approval; D004348:Drug Labeling; D004562:Electrocardiography; D006801:Humans; D007391:International Cooperation; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D017410:Practice Guidelines as Topic; D018570:Risk Assessment; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents