New Therapies Could Change Cancer Treatment Strategies

Armen Hareyan's picture
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The investigational drug AZD2171 (cediranib) may help shrink tumors and prolong survival of patients with a relatively common, aggressive type of brain cancer, according to results from a clinical trial conducted by Boston researchers.

In a phase II study of 31 patients with recurrent glioblastoma, researchers observed that daily treatment with cediranib decreased tumor volume by more than half in 56 percent of patients.

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. In addition, cediranib was found to alleviate brain swelling - a major cause of morbidity among these patients.

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

"These are promising, early results but are from a single study of 31 patients, so ongoing larger studies will be critical to determine if the findings are corroborated," said lead author Tracy Batchelor, M.D., M.P.H., executive director of the Stephen E. and Catherine Pappas Center for Neuro-Oncology at the Massachusetts General Hospital Cancer Center. "One important question is whether a combination of cediranib and chemotherapy will be more effective than cediranib alone. We have designed a randomized trial in patients with recurrent glioblastoma that will open at multiple sites in Europe, the U.S., Canada and Australia this summer that will address this and other questions."

Two of the 31 patients were removed from the current study because of toxicity (fatigue). However, dose reductions or 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 tumor progression and could be used to predict treatment failure in this study population, Batchelor says. 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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