Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs.

Autor:	Naing A; Departments of Investigational Cancer Therapeutics. Electronic address: anaing@mdanderson.org., Veasey-Rodrigues H; Departments of Investigational Cancer Therapeutics., Hong DS; Departments of Investigational Cancer Therapeutics., Fu S; Departments of Investigational Cancer Therapeutics., Falchook GS; Departments of Investigational Cancer Therapeutics., Wheler JJ; Departments of Investigational Cancer Therapeutics., Tsimberidou AM; Departments of Investigational Cancer Therapeutics., Wen S; Departments of Biostatistics., Fessahaye SN; Departments of Investigational Cancer Therapeutics., Golden EC; Departments of Investigational Cancer Therapeutics., Aaron J; Departments of Investigational Cancer Therapeutics., Ewer MS; Departments of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, USA., Kurzrock R; Departments of Investigational Cancer Therapeutics.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2012 Nov; Vol. 23 (11), pp. 2960-2963. Date of Electronic Publication: 2012 Jun 27.
DOI:	10.1093/annonc/mds130
Abstrakt:	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. Patients and 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. Conclusion: Frequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.
Databáze:	MEDLINE
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