Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model
- Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (United States)
- Department of Nutritional Sciences, University of Arizona, Tucson, AZ (United States)
- AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield (United Kingdom)
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA (United States)
Purpose: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. Methods and Materials: LoVo cells were injected subcutaneously into the right hind limb (5x10{sup 6} cells in 100muL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm{sup 3} before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3x3 Gy) on Days 1, 2, and 3. CPT-11 was given at 15 mg/kg intraperitoneally on Days 1 and 3. Tumor volumes were measured on a daily basis and calculated by measuring tumor diameters with digital calipers in two orthogonal dimensions. Results: All three single treatments (vandetanib, CPT-11, and radiation) significantly slowed LoVo colorectal tumor growth. Vandetanib significantly increased the antitumor effects of CPT-11 and radiation when given in combination with either of these treatments. These treatment combinations resulted in a slow tumor growth rate during the 2 weeks of vandetanib administration. The triple combination of vandetanib, CPT-11, and radiation produced the most marked improvement in response as observed by measurable shrinkage of tumors during the first week of treatment. Conclusions: The tumor growth delay kinetics observed in this study of the LoVo colorectal model suggest concurrent and sustained post-sequencing of vandetanib with cytotoxic therapy may be beneficial in tumors of this type.
- OSTI ID:
- 21362225
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2009.06.016; PII: S0360-3016(09)00917-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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