Document Detail


Cardiovascular toxicity profiles of vascular-disrupting agents.
MedLine Citation:
PMID:  21742963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Vascular-disrupting agents (VDAs) represent a new class of chemotherapeutic agent that targets the existing vasculature in solid tumors. Preclinical and early-phase trials have demonstrated the promising therapeutic benefits of VDAs but have also uncovered a distinctive toxicity profile highlighted by cardiovascular events.
METHODS: We reviewed all preclinical and prospective phase I-III clinical trials published up to August 2010 in MEDLINE and the American Association of Cancer Research and American Society of Clinical Oncology meeting abstracts of small-molecule VDAs, including combretastatin A4 phosphate (CA4P), combretastatin A1 phosphate (CA1P), MPC-6827, ZD6126, AVE8062, and ASA404.
RESULTS: Phase I and II studies of CA1P, ASA404, MPC-6827, and CA4P all reported cardiovascular toxicities, with the most common cardiac events being National Cancer Institute Common Toxicity Criteria (version 3) grade 1-3 hypertension, tachyarrhythmias and bradyarrhythmias, atrial fibrillation, and myocardial infarction. Cardiac events were dose-limiting toxicities in phase I trials with VDA monotherapy and combination therapy.
CONCLUSIONS: Early-phase trials of VDAs have revealed a cardiovascular toxicity profile similar to that of their vascular-targeting counterparts, the angiogenesis inhibitors. As these agents are added to the mainstream chemotherapeutic arsenal, careful identification of baseline cardiovascular risk factors would seem to be a prudent strategy. Close collaboration with cardiology colleagues for early indicators of serious cardiac adverse events will likely minimize toxicity while optimizing the therapeutic potential of VDAs and ultimately enhancing patient outcomes.
Authors:
Ishwaria M Subbiah; Daniel J Lenihan; Apostolia M Tsimberidou
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Publication Detail:
Type:  Journal Article     Date:  2011-07-08
Journal Detail:
Title:  The oncologist     Volume:  16     ISSN:  1549-490X     ISO Abbreviation:  Oncologist     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-29     Completed Date:  2012-02-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9607837     Medline TA:  Oncologist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1120-30     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / adverse effects*,  therapeutic use
Bibenzyls / adverse effects,  therapeutic use
Cardiovascular System / drug effects*
Clinical Trials as Topic
Humans
Neoplasms / blood supply*,  drug therapy*,  pathology
Neovascularization, Pathologic / drug therapy
Organophosphorus Compounds / adverse effects,  therapeutic use
Quinazolines / adverse effects,  therapeutic use
Serine / adverse effects,  analogs & derivatives,  therapeutic use
Xanthones / adverse effects,  therapeutic use
Chemical
Reg. No./Substance:
0/AC 7700; 0/Angiogenesis Inhibitors; 0/Bibenzyls; 0/N-acetylcochinol-O-phosphate; 0/Organophosphorus Compounds; 0/Quinazolines; 0/Xanthones; 0829J8133H/vadimezan; 56-45-1/Serine; 82855-09-2/combretastatin; X97O9FTB92/verubulin
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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