Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme.
BACKGROUND
Glioblastoma multiforme (GBM), a highly invasive and vascular cancer, responds poorly to conventional cytotoxic therapy. Integrins, widely expressed in GBM and tumor vasculature, mediate cell survival, migration and angiogenesis. Cilengitide is a potent alphavbeta3 and alphavbeta5 integrin inhibitor.


OBJECTIVE
To summarize the preclinical and clinical experience with cilengitide for GBM.


METHODS
Preclinical studies and clinical trials evaluating cilengitide for GBM were reviewed.


CONCLUSIONS
Cilengitide is active and synergizes with external beam radiotherapy in preclinical GBM models. In clinical trials for recurrent GBM, single-agent cilengitide has antitumor benefits and minimal toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating cilengitide into standard external beam radiotherapy/temozolomide have shown encouraging activity with no increased toxicity and have led to a planned randomized Phase III trial.
Reardon
David A
DA
Duke University Medical Center, Neuro-Oncology Program and Department of Surgery, Division of Neurosurgery, 047 Baker House, Box 3624, Durham, North Carolina, 27710, USA. reard003@mc.duke.edu
Nabors
L Burt
LB
Stupp
Roger
R
Mikkelsen
Tom
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008958:Models, Molecular; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011485:Protein Binding; D012910:Snake Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016023:Integrins; D009842:Oligopeptides; D012910:Snake Venoms; C422910:Cilengitide; C047981:arginyl-glycyl-aspartic acid