Document Detail

VEGF-associated tyrosine kinase inhibition increases the tumor response to single and fractionated dose radiotherapy.
MedLine Citation:
PMID:  16751064     Owner:  NLM     Status:  MEDLINE    
PURPOSE: In this study, the efficacy of combining ZD6474 (Zactima), a vascular endothelial growth factor (VEGF) receptor 2-associated tyrosine kinase inhibitor currently undergoing Phase II clinical trial evaluation, with single and fractionated dose radiation exposures was examined in a human colorectal carcinoma model (HT29). METHODS AND MATERIALS: HT29 xenograft-bearing mice were treated with either single-dose (10 Gy) or multifraction (2 Gy/day for 2 weeks) radiotherapy alone or in conjunction with a 2-week course of ZD6474 (25 mg/kg). In the single-dose investigation, ZD6474 treatment followed radiotherapy, whereas in the fractionated dose studies the antiangiogenic therapy was given before, after, or concurrent with the radiation. Tumor response was determined by tumor growth delay. RESULTS: ZD6474 increased the response of HT29 xenografts to both single and fractionated dose radiotherapy. In the fractionation studies sequencing of therapies had little impact on treatment outcomes; the time for the median tumors in each of the treatment groups to grow to five times the starting size was 53, 53.5, and 49 days, respectively. CONCLUSIONS: These studies indicate that ZD6474, when used in conjunction with radiation therapy, has a clear therapeutic advantage, providing a rationale for considering the combination of this agent with radiotherapy in the clinic.
William D Brazelle; Wenyin Shi; Dietmar W Siemann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  65     ISSN:  0360-3016     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-05     Completed Date:  2006-07-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  836-41     Citation Subset:  IM    
Department of Radiation Oncology, Shands Cancer Center, University of Florida, Gainesville, FL, USA.
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MeSH Terms
Angiogenesis Inhibitors / therapeutic use*
Colorectal Neoplasms / drug therapy*,  radiotherapy*
Combined Modality Therapy / methods
Enzyme Inhibitors / therapeutic use*
HT29 Cells
Mice, Inbred Strains
Mice, Nude
Piperidines / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Quinazolines / therapeutic use*
Radiotherapy Dosage
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Grant Support
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Enzyme Inhibitors; 0/N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine; 0/Piperidines; 0/Quinazolines; EC Kinases; EC Endothelial Growth Factor Receptor-2

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