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Avastin + Chemo for Advanced Pancreatic Cancer?

We’ve watched with interest as the pendulum has swung back and forth over the years on the possible efficacy of agents (for pancreatic cancer) that block Vascular Endothelial Growth Factor (VEGF), a molecule that mediates angiogenesis (the vascular growth that occurs in tumors). Bevacizumab, a monoclonal antibody to VEGF, is known as Avastin and is manufactured by Genentech. It is approved in distinct circumstances for the treatment of colorectal, lung, kidney and brain cancers. One of Avastin’s side-effects in certain patients is high blood pressure.

The idea of Avastin is to interfere with the mechanism that allows for pancreatic cancer tumor (ductal adenocarcinoma of the pancreas) growth and spread.

Researchers from Ohio State University recently published a study in the Annals of Oncology where they described their Phase II study that included adding bevacizumab to gemcitabine followed by an infusion of 5-FU to about forty patients with advanced pancreatic cancer. The progression-free survival at six months in this group was found to be 49% of the evaluable patients – which met their endpoint hypothesis of > 41%. They recommend further testing with this regimen in advanced pancreatic cancer “in combination with fluoropyrimidine-based therapy” (that is: 5-FU like). And they added an interesting side note suggestion for future researchers to see if the development of high blood pressure with this regimen (presumably from the Avastin) might be a sign of greater efficacy for those individual patients who do respond.

A past study which had not been so kind to the use of Avastin in pancreatic cancer was the Phase III trial of the Cancer and Leukemia Group B, reported out in the Journal of Clinical Oncology in August, 2010 with a conclusion, “The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients.”

It is an interesting distinction: Avastin plus gemcitabine (2010 study – not promising) versus Avastin (plus gemcitabine) plus 5-FU (more promising results) for advanced pancreatic cancer.

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Dale O’Brien, MD