Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

Phyllis Wachsberger, Randy M Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 (5×106 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3×3 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.

Original languageEnglish (US)
Pages (from-to)854-861
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume75
Issue number3
DOIs
StatePublished - Nov 1 2009

Fingerprint

irinotecan
Heterografts
Colorectal Neoplasms
radiation therapy
Radiotherapy
tumors
cancer
Neoplasms
Radiation
Growth
Therapeutics
therapy
radiation
Receptor Protein-Tyrosine Kinases
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Tumor Burden
sequencing
tyrosine

Keywords

  • Angiogenesis inhibitor
  • CPT-11
  • LoVo colorectal cancer
  • Radiotherapy
  • Vandetanib

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model. / Wachsberger, Phyllis; Burd, Randy M; Ryan, Anderson; Daskalakis, Constantine; Dicker, Adam P.

In: International Journal of Radiation Oncology Biology Physics, Vol. 75, No. 3, 01.11.2009, p. 854-861.

Research output: Contribution to journalArticle

Wachsberger, Phyllis ; Burd, Randy M ; Ryan, Anderson ; Daskalakis, Constantine ; Dicker, Adam P. / Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model. In: International Journal of Radiation Oncology Biology Physics. 2009 ; Vol. 75, No. 3. pp. 854-861.
@article{fb044fe53dfd41dda956a7dd38ca4e6f,
title = "Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model",
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 (5×106 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3×3 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.",
keywords = "Angiogenesis inhibitor, CPT-11, LoVo colorectal cancer, Radiotherapy, Vandetanib",
author = "Phyllis Wachsberger and Burd, {Randy M} and Anderson Ryan and Constantine Daskalakis and Dicker, {Adam P.}",
year = "2009",
month = "11",
day = "1",
doi = "10.1016/j.ijrobp.2009.06.016",
language = "English (US)",
volume = "75",
pages = "854--861",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

AU - Wachsberger, Phyllis

AU - Burd, Randy M

AU - Ryan, Anderson

AU - Daskalakis, Constantine

AU - Dicker, Adam P.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - 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 (5×106 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3×3 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.

AB - 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 (5×106 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3×3 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.

KW - Angiogenesis inhibitor

KW - CPT-11

KW - LoVo colorectal cancer

KW - Radiotherapy

KW - Vandetanib

UR - http://www.scopus.com/inward/record.url?scp=70349546300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349546300&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2009.06.016

DO - 10.1016/j.ijrobp.2009.06.016

M3 - Article

C2 - 19801101

AN - SCOPUS:70349546300

VL - 75

SP - 854

EP - 861

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 3

ER -