We’ve watched with interest as the pendulum has swung back and forth over the years on the possible efficacy of agents 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 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 add 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.
A past study which had not been so kind to the use of Avastin was the Phase III trial of the Cancer and Leukemia Group B, reported out in the Journal of Clinical Oncology in August, 2010.
“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 (current more promising results) for advanced pancreatic cancer.
Dale O’Brien, MD
There has not been very much study on when “adjuvant” chemotherapy should begin after pancreatic cancer surgery (this process of chemo AFTER surgery is called adjuvant therapy). What is known is that adjuvant chemotherapy tends to confer a significant survival boost to pancreatic cancer patients. And perhaps it is fair to say that it has generally been assumed as to the timing of the start of this chemotherapy – that it should begin after the immediate effects of surgery have been weathered by the patient – and when that the patient is well enough to begin to accept the side-effects of the chemo. But, does this timing have more significance than is generally believed?
Sueda and associates from Hiroshima University in Japan recently reviewed the records of 104 patients who received chemotherapy after potentially curable surgery in pancreatic cancer – dividing the patients into two groups: those who began the chemo more than or less than 20 days after the day of the pancreatic cancer surgery. They found that those who had received the chemotherapy earlier in the process had significantly better 5-year survival rates (52% vs. 26%). One factor of note is that the early chemo group tended to have had fewer after-surgery complications. So, might these surgical complications be a tell – that the later group was not as predisposed to survival? In any case, this surprising finding is worth considering – and deserves more study.
Dale O’Brien, MD
Those of a certain age will remember the terrible congenital malformations fifty years on due to the prenatal use of thalidomide. Gradually in certain circumstances thalidomide use has made a cautious comeback in medicine – now including for pancreatic cancer.
Chinese researchers from Shang Dong Tumor Hospital in Jinan, China have published an interesting Phase II clinical study in the November issue of Pancreatology that looked at capecitabine (Xeloda) in combination with thalidomide as a possible second-line treatment for advanced pancreatic cancer in those who were refractory to gemcitabine treatment. Their conclusion was that this combination was reasonably well tolerated, and showed reasonable response in certain pancreatic cancer patients with advanced disease. Of 31 patients, two demonstrated a partial response and eleven patients showed stable disease.
Sometimes you can use an old dog for new tricks.
Dale O’Brien, MD