Abstract
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 αvβ3 and αvβ5 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. Results/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.
Original language | English (US) |
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Pages (from-to) | 1225-1235 |
Number of pages | 11 |
Journal | Expert Opinion on Investigational Drugs |
Volume | 17 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2008 |
Funding
T Mikkelsen has received research funding from Merck KGaA. LB Nabors has served on the advisory board for Merck, has received honorarium and has contributed to the writing. R Stupp has acted as a consultant for Merck KGaA sponsored trials and has received honoraria. This study was supported by National Institutes of Health grant nos. 1-P50-CA108786-01, NS20023, and CA11898 and by grant no. MO1 RR 30 through the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.
Keywords
- Angiogenesis
- Glioblastoma multiforme
- Integrins
- Malignant glioma
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology