Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs. Ann Oncol 2012 Nov;23(11):2960-2963
Date
06/30/2012Pubmed ID
22745218Pubmed Central ID
PMC4092255DOI
10.1093/annonc/mds130Scopus ID
2-s2.0-84868113707 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Naing A, Veasey-Rodrigues H, Hong DS, Fu S, Falchook GS, Wheler JJ, Tsimberidou AM, Wen S, Fessahaye SN, Golden EC, Aaron J, Ewer MS, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Antineoplastic Agents
Clinical Trials, Phase I as Topic
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Electrocardiography
Female
Heart
Heart Rate
Humans
Long QT Syndrome
Male
Middle Aged
Neoplasms
Young Adult
