ARBs and ACE inhibitors could improve survival in pancreatic cancer

"Medications for hypertension do not have a lot of side effects – far fewer than chemotherapy, for example – and yet our data suggests that they might extend life in patients with pancreatic cancer," says first author Scott Keith, PhD, associate professor of Biostatistics at Thomas Jefferson University. "Clinical studies will be required to explore just how much these approved and inexpensive therapies can extend life, and our data make a strong case for investing in further research."

The researchers led by Dr. Keith and Vittorio Maio, a professor in the College of Population Health and managing director of the Asano-Gonnella Center for Research in Medical Education and Health Care at Jefferson, examined a dataset of 3.7 million adults living in Northern Italy. A total of 8,158 pancreatic cancer patients were identified between 2003 and 2011 from this region. The health records from this national database allowed the researchers to look at a patient's full medical record over time and match comparison groups by age, gender, additional medication usage and other variables. The team was able to compare pancreatic cancer patients to those who had taken hypertension medication in addition to their cancer therapy, and model or predict the risk of mortality by group.

Earlier research in animals suggested that ARB-type therapies – which include drugs such as valsartan and losartan – and ACE inhibitors – including benazepril, ramipril or Lisinopril – might slow pancreatic cancer growth. Several small clinical trials suggested the same effect, although the numbers of patients in those studies was too small to draw broad conclusions. These two medications interact with the angiotensin system, which is normally responsible for narrowing blood vessels, but have also been shown to interact with cancer-growth pathways.

Drs. Keith and Maio's analysis is the largest retrospective study to look at pancreatic patient survival as it relates to ARB- and ACE-inhibitor usage. That was possible because of the availability of a comprehensive, population-based longitudinal healthcare database from a public healthcare system.

Their results showed that the group of pancreatic cancer patients who also took ARB class of drugs had a 20% lower in risk of mortality, and a 28% lower risk for patients who had been treated with surgery for their cancer. Those taking the ACE inhibitors saw a 13% reduction in risk of mortality in the first three years after diagnosis.

"We can't predict how much these medications can extend life," says Dr. Maio. "A randomized clinical trial would be necessary to determine that benefit. But this data does suggest that people with pancreatic cancer who are taking ARB or ACE inhibitors are living longer than those who aren't."

"We think this data strongly support investing in a clinical study that could extend patient lives using an inexpensive, safe, medication," says Dr. Keith. "We will urge institutions, cancer organizations and the pharmaceutical industry to set up a collaborative and well-resourced initiative to study the potential therapeutic effect of these inexpensive antihypertensive medications on pancreatic cancer patients," added Dr. Maio.

This study was supported, in part, by an Institutional Research Grant (IRG-08-060-04) from the American Cancer Society. The authors report no conflicts of interest.