Angiogenic inhibitors: A new therapeutic strategy in oncology

Giampietro Gasparini, Raffaele Longo, Masakazu Toi, Napoleone Ferrara

Research output: Contribution to journalArticle

Abstract

Angiogenesis is a multistep, complex and tightly regulated process that is necessary for tumor growth and metastasis. Based on data of preclinical models, several antiangiogenic compounds has been shown to modify activated tumor endothelium, which suggests that these compounds can improve cytotoxic drug delivery. Such agents have entered clinical trials as single agents or in combination with cytotoxic drugs, and have shown promising antitumor activity. The pharmacodynamic and pharmacokinetic characteristics of antiangiogenic drugs are reviewed here. Most of the early clinical testing of these agents was conducted in patients with advanced disease resistant to standard therapies. Phase III trials compared the efficacy of standard chemotherapy alone with standard chemotherapy in combination with an experimental angiogenesis inhibitor. Although some of these studies were negative or controversial, recent studies validated in large clinical trials with an anti-vascular endothelial growth factor antibody demonstrated significant clinical benefit and renewed enthusiasm for this therapeutic strategy. This review describes the clinical studies of antiangiogenic agents and highlights the challenges related to choosing appropriate strategies for the selection of patients, study design and choice of appropriate endpoints for the studies' development.

Original languageEnglish
Pages (from-to)562-577
Number of pages16
JournalNature Clinical Practice Oncology
Volume2
Issue number11
DOIs
Publication statusPublished - Nov 2005

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Keywords

  • Antiangiogenic therapy
  • Bevacizumab
  • SU11248
  • Tyrosine kinase inhibitors
  • VEGF

ASJC Scopus subject areas

  • Oncology

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