Angiogenic inhibitors: a new therapeutic strategy in oncology.
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.
Gasparini
Giampietro
G
Division of Medical Oncology, San Filippo Neri Hospital, Via G Martinotti, 20 00135 Rome, Italy. gasparini.oncology@tiscalinet.it
Longo
Raffaele
R
Toi
Masakazu
M
Ferrara
Napoleone
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic; D012107:Research Design; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab