This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strevel, E. L. Articles by Siu, L. L. Search for Related Content PubMed PubMed Citation Articles by Strevel, E. L. Articles by Siu, L. L. Social Bookmarking                            What's this?

Molecularly Targeted Oncology Therapeutics and Prolongation of the QT Interval

Elizabeth L. Strevel, Douglas J. Ing, Lillian L. Siu

From the Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network; Division of Cardiology, Toronto General Hospital, University Health Network; and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Address reprint requests to Lillian L. Siu, MD, FRCPC, Princess Margaret Hospital, Division of Medical Oncology and Hematology, 610 University Ave, Suite 5-718, Toronto, ON, Canada M5G 2M9; e-mail: lillian.siu{at}uhn.on.ca

Investigation and utilization of molecularly targeted agents has induced a number of drug adverse effects that are not typically associated with conventional chemotherapy. QT interval prolongation, a cardiac toxicity that increases the risk of fatal arrhythmia, is associated with several novel oncology therapies. Classes of molecularly targeted agents with described QT effects include histone deacetylase inhibitors, multitargeted tyrosine kinase inhibitors, vascular disruption agents, farnesyl protein transferase inhibitors, Src/Abl kinase inhibitors, and protein kinase C inhibitors. Concurrently, guidelines for monitoring the QT-prolonging effects of drugs under development have become increasingly rigorous. Although these guidelines apply to anticancer agents, they were not specifically designed for the oncology patient population. This article will review the pathophysiology of QT prolongation, methods of preclinical QT assessment, and current guidelines for QT evaluation in early phase trials. Additionally, molecularly targeted agents with QT effects will be summarized, and mechanisms of addressing this toxicity in the context of oncology drug development will be explored.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. L. Bello, M. Mulay, X. Huang, S. Patyna, M. Dinolfo, S. Levine, A. Van Vugt, M. Toh, C. Baum, and L. Rosen Electrocardiographic Characterization of the QTc Interval in Patients with Advanced Solid Tumors: Pharmacokinetic- Pharmacodynamic Evaluation of Sunitinib Clin. Cancer Res., November 15, 2009; 15(22): 7045 - 7052. [Abstract] [Full Text] [PDF]

				A. A. Lane and B. A. Chabner Histone Deacetylase Inhibitors in Cancer Therapy J. Clin. Oncol., November 10, 2009; 27(32): 5459 - 5468. [Abstract] [Full Text] [PDF]

				B. Glimelius, M. Lahn, S. Gawande, A. Cleverly, C. Darstein, L. Musib, Y. Liu, K. L. Spindler, J.-E. Frodin, A. Berglund, et al. A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer Ann. Onc., November 9, 2009; (2009) mdp521v1. [Abstract] [Full Text] [PDF]

				A. Badros, A. M. Burger, S. Philip, R. Niesvizky, S. S. Kolla, O. Goloubeva, C. Harris, J. Zwiebel, J. J. Wright, I. Espinoza-Delgado, et al. Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple Myeloma Clin. Cancer Res., August 15, 2009; 15(16): 5250 - 5257. [Abstract] [Full Text] [PDF]

				E. T.H. Yeh and C. L. Bickford Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J. Am. Coll. Cardiol., June 16, 2009; 53(24): 2231 - 2247. [Abstract] [Full Text] [PDF]

				L. Zhang, D. Lebwohl, E. Masson, G. Laird, M. R. Cooper, and H. M. Prince Clinically Relevant QTc Prolongation Is Not Associated With Current Dose Schedules of LBH589 (panobinostat) J. Clin. Oncol., January 10, 2008; 26(2): 332 - 333. [Full Text] [PDF]

				E. L. Strevel and L. L. Siu In Reply J. Clin. Oncol., January 10, 2008; 26(2): 333 - 334. [Full Text] [PDF]

				A. Saad, R. Beto, J. Abraham, and S. C. Remick Cardiovascular Safety and Toxicity Profile of New Molecularly Targeted Anticancer Agents ASCO Educational Book, January 1, 2008; 2008(1): 428 - 434. [Abstract] [Full Text] [PDF]