Challenges of characterizing proarrhythmic risk due to QTc prolongation induced by nonadjuvant anticancer agents.
Expert Opin Drug Saf. 2008 May;7(3):305-18
Authors: Sarapa N, Britto MR
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. CONCLUSION: 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.
PMID: 18462188 [PubMed - indexed for MEDLINE]
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