Research article summary (published 30 Oct 2009):

Combination of vandetanib, radiotherapy, and irinotecan in the LoVo human colorectal cancer xenograft model.

Full Abstract

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 (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(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 (3 x 3 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.

Author information

Author/s: Wachsberger, Phyllis (P); Burd, Randy (R); Ryan, Anderson (A); Daskalakis, Constantine (C); Dicker, Adam P (AP);

Affiliation: Department of Radiation Oncology, Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA 19107, USA. Phyllis.wachsberger(-atsign-)jeffersonhospital.org

Grants: CA 10663 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys), published in United States. (Language: eng)

Reference: 2009-Nov; vol 75 (issue 3) : pp 854-61

Dates: Created 2009/10/05; Completed 2009/10/20;

PMID: 19801101, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Angiogenesis Inhibitors - therapeutic use Animals Antineoplastic Agents, Phytogenic - therapeutic use Camptothecin - analogs & derivatives; therapeutic use Colorectal Neoplasms - drug therapy; pathology; radiotherapy Combined Modality Therapy - methods Dose Fractionation Humans

Mice Mice, Nude Piperidines - therapeutic use Protein Kinase Inhibitors - therapeutic use Quinazolines - therapeutic use Receptor, Epidermal Growth Factor Tumor Burden Xenograft Model Antitumor Assays

Associated Chemicals: Angiogenesis Inhibitors (0) ; Antineoplastic Agents, Phytogenic (0) ; N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine (0) ; Piperidines (0) ; Protein Kinase Inhibitors (0) ; Quinazolines (0) ; irinotecan (100286-90-6) ; Camptothecin (7689-03-4) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112)

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