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Update on Anti-angiogenesis Therapy in Colorectal Cancer

  • Translational Colorectal Oncology (Y Jiang, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil-, leucovorin-, and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin, and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin-, and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost-effectiveness of these anti-angiogenic agents and others are as yet unanswered.

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Abbreviations

5-FU :

5-Fluorouracil

ALK :

Activin-receptor like kinase-1

BEAMing :

Beads, emulsions, amplification and magnetic

CI :

Confidence interval

CRC :

Colorectal cancer

DCE-MRI :

Dynamic-contrast-enhanced magnetic resonance imaging

DCR :

Disease control rate

DFS :

Disease-free survival

DLT :

Dose-limiting toxicity

DVT :

Deep venous thrombosis

EGFR :

Epidermal growth factor receptor

FGFR :

Fibroblast growth factor receptor

FDA :

Food and Drug Administration

FOLFOX :

5-Fluorouracil, leucovorin, and oxaliplatin

FOLFOX4 :

Oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 400 mg/m2 bolus plus 500 mg/m2 22-h continuous infusion on day1; leucovorin 200 mg/m2 plus fluorouracil 400 mg/m2 bolus plus 600 mg/m2 22-h continuous infusion on day 2

FOLFIRI :

5-Fluorouracil, leucovorin and irinotecan

HR :

Hazard ratio

ICER :

Incremental cost-effectiveness ratio

IFL :

Irinotecan, bolus fluorouracil, and leucovorin

IV :

Intravenous

KRAS :

Kirsten ras oncogene

mCRC :

Metastatic colorectal cancer

mFOLFOX6 :

Modified FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 bolus, and 5-FU2400 mg/m2 over 46 h)

MTD :

Maximum tolerated dose

NICE :

National Institute for Health and Care Evidence

NSABP :

National Surgical Adjuvant Breast and Bowel Project

ORR :

Overall response rate

OS :

Overall survival

PDGFR :

Platelet-derived growth factor receptor

PR :

Partial response

PlGF :

Placental growth factor

PFS :

Progression-free survival

SD :

Stable disease

TBD :

To be determined

VEGF :

Vascular endothelial growth factor

XELOX :

Capecitabine and oxaliplatin

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Conflict of Interest

Kristen K. Ciombor declares that she has no conflict of interest.

Richard M. Goldberg has received research support through grants for a clinical trial from Sanofi and Bayer to The Ohio State University and has received compensation from Eli Lilly & Co. for service on a data safety monitoring committee for a clinical trial and from Sanofi for conducting a lecture at a symposium.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital & Richard J. Solove Research Institute, A445A Starling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA

    Kristen K. Ciombor

  2. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital & Richard J. Solove Research Institute, 460 West 10th Avenue, Suite D920, Columbus, OH, 43210, USA

    Richard M. Goldberg

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  1. Kristen K. Ciombor
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Correspondence to Richard M. Goldberg.

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Topical Collection on Translational Colorectal Oncology

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Ciombor, K.K., Goldberg, R.M. Update on Anti-angiogenesis Therapy in Colorectal Cancer. Curr Colorectal Cancer Rep 11, 378–387 (2015). https://doi.org/10.1007/s11888-015-0292-3

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