Review
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World J Exp Med. Nov 20, 2014; 4(4): 58-67
Published online Nov 20, 2014. doi: 10.5493/wjem.v4.i4.58
Combinations of vascular endothelial growth factor pathway inhibitors with metronomic chemotherapy: Rational and current status
Antonia Digklia, Ioannis A Voutsadakis
Antonia Digklia, Department of Medical Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland
Ioannis A Voutsadakis, Division of Medical Oncology, Department of Internal Medicine, Sault Area Hospital, Sault Sainte Marie, Ontario, ON P6B 0A8, Canada
Ioannis A Voutsadakis, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, ON P6B 0A8, Canada
Author contributions: Both authors contributed to this paper.
Correspondence to: Ioannis A Voutsadakis, MD, PhD, Division of Clinical Sciences, Northern Ontario School of Medicine, 750 Great Northern Road, Sault Ste Marie, Sudbury, Ontario, ON P6B 0A8, Canada. ivoutsadakis@yahoo.com
Telephone: +1-705-7593434 Fax: +1-705-7593815
Received: June 11, 2014
Revised: July 16, 2014
Accepted: September 6, 2014
Published online: November 20, 2014
Abstract

Chemotherapy given in a metronomic manner can be administered with less adverse effects which are common with conventional schedules such as myelotoxicity and gastrointestinal toxicity and thus may be appropriate for older patients and patients with decreased performance status. Efficacy has been observed in several settings. An opportunity to improve the efficacy of metronomic schedules without significantly increasing toxicity presents with the addition of anti-angiogenic targeted treatments. These combinations rational stems from the understanding of the importance of angiogenesis in the mechanism of action of metronomic chemotherapy which may be augmented by specific targeting of the vascular endothelial growth factor (VEGF) pathway by antibodies or small tyrosine kinase inhibitors. Combinations of metronomic chemotherapy schedules with VEGF pathway targeting drugs will be discussed in this paper.

Keywords: Metronomic chemotherapy, Vascular endothelial growth factor, Angiogenesis, Bevacizumab, Vascular endothelial growth factor receptor

Core tip: Metronomic chemotherapy has the potential to reduce the toxicity of chemotherapy administered with conventional schedules. In addition, understanding of the importance of angiogenesis in the mechanism of action of metronomic schedules provides a rational to combine this type of administration with targeted agents against the vascular endothelial growth factor signaling pathway.