Monday, July 14, 2008

Cediranib (AZD2171) in Glioblastoma and brain cancer

The investigational drug AZD2171 (cediranib) from Astra-Zeneca may help shrink tumours and prolong survival of patients with a relatively common, aggressive type of brain cancer. In a phase II study of 31 patients with recurrent glioblastoma, researchers observed that daily treatment with cediranib decreased tumour volume by more than half in 56 percent of patients. These results were reported at the recent AACR meeting.

Nearly 26 percent of patients were alive and their cancer had not progressed six months into treatment. On average, patients experienced a progression-free survival of 117 days and overall survival of 221 days. Cediranib was also found to alleviate brain swelling, a major cause of morbidity among these patients.

Cediranib is a selective signaling inhibitor for vascular endothelial growth factor (VEGF), which promotes formation of new blood vessels that tumours need for nourishment and growth. The drug targets all three receptors for VEGF, one of which is expressed on the endothelial cells in glioblastoma.

Two of the 31 patients were removed from the current study because of toxicity (fatigue). Dose reductions, ie short breaks from the drug, were required for most patients, usually due to hypertension, diarrhea and fatigue.

By analyzing blood samples from patients, the researchers found that the biomarkers FGF (fibroblast growth factor) and Tie-2 were associated with tumour progression and could be used to predict treatment failure in this study population. FGF is a protein tied to new blood vessel growth; Tie-2 is a receptor that binds to and is activated by the angiopoietins - protein growth factors required for the formation of blood vessels.

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