“Half the lies they tell about me aren’t true.” -Yogi Berra
There are legitimate controversies in pancreatic cancer. Often over time, the pendulum can swing to one side or the other of a scientific conflict – as new evidence supports a contention or not. Sometimes, with a greater understanding of the complexity of an issue, both sides can even turn out to be right – or wrong.
For example, one legitimate controversy that has been raging for over a decade now, is whether adding radiation to chemotherapy will help increase patient survival after receiving surgery for pancreatic cancer (adjuvant chemoradiation). There are some interesting recent studies on this topic but the issue is not yet resolved or fully teased out.
Below are discussions of recent studies on THREE such issues that have been matters of some inquiry and even controversy. These results are not presented as definitive (as the pendulum never fully settles in real science) but they are fairly compelling – for now.
We should probably herewith highly complement the authors of these studies – as often studies that don’t show a “positive” outcome tend NOT to get published. This phenomenon results in what is called publication bias, and represents a skewing of reality through an inadvertent withholding of what is deemed worthy of being published – and therefore distorts the meaning of the medical literature. Increasingly, we at Pancreatica have noticed that authors have more recently been bucking this trend, and commendably have started often publishing studies that do not have what are seen as positive results.
Coffee intake is not a causative element for pancreatic cancer European and Malaysian researchers published work in the November 2013 issue of Clinical Gastroenterology and Hepatology, the journal of the American Gastroenterological Association. The researchers examined data from the European Prospective Investigation into Nutrition and Cancer, and found no association between coffee, decaffeinated coffee or tea intake and the risk of pancreatic cancer.
Helicobacter pylori (bacteria) is not a cause of pancreatic cancer Researchers from the Division of Cancer Epidemiology and Genetics of the U.S. National Cancer Institute E-published an article on October 2, 2013 for the journal Cancer Epidemiology, Biomarkers & Prevention, a publication (in part) of the American Association for Cancer Research. These authors in a nested case-control study looked at a group of Finnish males in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and found no association between H. pylori antigen status (bacteria associated with peptic ulcer disease) in the subjects’ serum and the risk of pancreatic cancer.
Metformin exposure does not increase survival in pancreatic cancer Yang and colleagues from the University of Pennsylvania published the results of a retrospective cohort study in the October issue of the journal Pancreas using data from The Health Improvement Network. The authors found that there was no difference of overall survival in those with pancreatic cancer who were exposed or not exposed to the diabetes drug: metformin.
More here (coffee)
More here (H. pylori)
More here (metformin)
Dale O’Brien, MD
As noted in an earlier blog, GVAX is a kind of vaccine that appears to work by enhancing “granulocyte-macrophage colony-stimulating factor” (GM-CSF) which in turn enhances white blood cells including monocytes that can somewhat freely move and have the ability to transform into so-called “professional” antigen-presenting cells such as macrophages and dendritic cells – which can augment the internal immune system’s own ability to fight cancer.
We were alerted to recent GVAX work by David Desert, and want to thank him for this. In an article first presented by electronic release on September 18, 2013, Laheru and colleagues from Johns Hopkins University published work in the Annals of Surgical Oncology that noted a possible relationship between hematologic status and survival in patients with pancreatic cancer who had received treatment with GVAX.
The researchers studied 59 pancreatic cancer patients in an existing Phase II clinical trial who received adjuvant chemoradiation plus GVAX after initial surgery. The Hopkins team found that those who carried a baseline total lymphocyte count of less than 1,500 cells per mm³ were at higher risk of poor overall survival and of progression-free survival. The authors also found that the chemoradiation treatment significantly reduced lymphocyte counts from baseline levels, and that those patients with such suppression to lower than 500 cells per mm³ were also at a disadvantage in terms of overall survival and of progression-free survival.
This is an interesting study that links potential efficacy of treatment (or lack thereof) with immunologic therapy under conditions of immunosuppression. These are early findings with a number of potential confounders, but nonetheless a highly interesting study result.
Dale O’Brien, MD
FDA Grants Orphan Status for CRS-207 (Mesothelin Targeting Vaccine) in Sequence with GVAX Immunotherapy
In an interesting step with intriguingly complex promise, the Office of Orphan Products Development of the U.S. Food and Drug Administration recently designated the immunotherapy CRS-207 as having orphan drug status for use in sequential combination with the GVAX Pancreas biologic for the treatment of pancreatic cancer. Both of these immunotherapeutic agents are owned by Aduro BioTech Inc. of Berkeley, California.
This move by the FDA coincides with Aduro having recently completed a randomized controlled Phase II clinical trial of patients with metastatic pancreatic cancer with this regimen (as yet unpublished), and appears to have sprung from the earlier work of Laheru and colleagues at Johns Hopkins University pursuant to a study published in the February 2012 issue of Clinical Cancer Research, the official journal of the American Association For Cancer Research. In this earlier Phase I research study, three of the patients with pancreatic cancer who had been earlier treated with GVAX appeared to show disease stability after the addition of further immunotherapy that included CRS-207.
Although vaccines and immunotherapies have been an interesting concept in theory generally in cancer and specifically in pancreatic cancer – there have been no clear breakthroughs.
CRS-207 is a live but attenuated Listeria monocytogenes strain that is aimed to induce an immunologic response specific to the antigen: mesothelin – which tends to be over-expressed in pancreatic adenocarcinoma. GVAX is a biologic that stimulates “granulocyte-macrophage colony-stimulating factor” (GM-CSF), boosting white cells including monocytes that roam and can mature into macrophages and dendritic cells – which augment the immune system’s ability to fight cancer.
In February 2013, Aduro purchased GVAX from BioSante Pharmaceuticals, Inc. Drew Pardoll, MD, PhD of Johns Hopkins University is the Chairman of the Scientific Advisory Board of Aduro BioTech. He and other researchers from Johns Hopkins have been involved in research with GVAX and pancreatic cancer for over a decade.
This 1-2 punch (CRS-207 / GVAX) at different areas of the immunologic / inflammatory cascade is a clever and promising idea. It will be interesting to see the results of the Phase II work, and to follow the results of this novel and creative line of study.
Dale O’Brien, MD