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Statins & Metformin Help Pancreatic Cancer Patients

Susman, Ed

doi: 10.1097/01.COT.0000484654.88171.66
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pancreatic cancer
pancreatic cancer:
pancreatic cancer

SAN FRANCISCO—A diagnosis of pancreatic cancer can be devastating, but there are factors that give some of these patients a fighting chance—including taking the anti-cholesterol statins (Abstract 427) and the anti-diabetes drug metformin (Abstract 383). Researchers also said being in better physical condition—particularly not being diagnosed with sarcopenia (Abstract 415)—is associated with better survival.

“Statins are likely to help in any kind of cancer because they have anti-inflammatory properties,” said Brian Huang, MPH, a PhD student at the University of California at Los Angeles. “The take-home message here is that statins are a pretty good thing to be on if you have cancer.”

Overall, being on a statin was associated with a 28 percent decreased risk of mortality. “Specifically,” Huang told Oncology Times at his poster presentation, “those who had used statins for 9-12 months and received higher doses had improved survival compared with non-users.”

He reported on outcomes among 2,142 pancreatic ductal adenocarcinoma patients who had been diagnosed between 2006 and 2014 in the Kaiser Permanente Southern California system. Of that group, 1,015 patients were not taking statins at the time of diagnosis; 1,127 were on various statin products, most frequently simvastatin (Zocor).

“Patients on simvastatin had a 31 percent decreased risk of mortality (P<0.0001),” said Huang, who is also a biostatistician at Kaiser Permanente. There were 680 patients in the study who were on simvastatin. The researchers also found atorvastatin (Lipitor) was associated with a 39 percent lower risk of mortality (P<0.01), but just 149 patients were taking that drug. No other statin achieved statistical significance in reducing the mortality risk from pancreatic cancer in the Kaiser database.

Higher levels of statin use—more than 40 mg a day—were also associated with a significant reduction in the risk of mortality, Huang reported. “Cholesterol control did not influence the relationship between statins and mortality, suggesting that statins improve survival through a lipid-independent pathway,” he said.

The research team also found statins were more successful in reducing the risk of mortality in patients with early stage disease—stage 1,2, or 3, compared with patients having distant disease. However, the early stage pancreatic cancer was found in 975 patients characterized with localized or regional cancer compared with 1,167 patients who were diagnosed initially with distant disease.

Treatment With Metformin

In another study, researchers at the Icahn School of Medicine at Mount Sinai, New York, reported patients with pancreatic ductal adenocarcinoma who were on metformin had a significantly longer survival when compared with patients who were not taking metformin at the time of diagnosis. The mean survival was 5.5 months for patients on metformin and 4.2 months for those not on the drug that controls blood sugar (P<0.01), said Aimee Lucas, MD, Assistant Professor of Gastroenterology at Mount Sinai.

“We specifically were looking at patients who were diagnosed with diabetes before they were diagnosed with pancreatic cancer,” she said. “You can get diabetes from developing pancreatic cancer, and if you remove the pancreas as part of treatment you will become diabetic. We wanted to specifically narrow out group to type 2 diabetes.”

“The one-month survival advantage sounds pretty terrible, but for pancreatic cancer it actually is pretty good,” Lucas told Oncology Times. Survival was dependent upon stage at diagnosis, with stage 1 patients living an average of almost 3 months longer if they were on metformin. Although that difference didn't reach statistical significance (P=0.08), she suggested it was a sample size issue.

She also noted that being on metformin was beneficial at every stage of diagnosis, although at stage 4 the difference was a matter of weeks—2.9 months compared with 2.4 months for those not on metformin, but still a significant difference (P<0.01). “Stage 4 pancreatic cancer just has very poor overall survival,” Lucas said.

She reported that taking metformin offered a 12 percent reduction in risk of mortality. The researchers also observed treatment with other anti-diabetes medications did not have a statistically significant benefit in reducing mortality risk; but being on insulin appeared to be detrimental to survival with those on insulin having a mean survival of 4.3 months compared with a mean survival of 5.5 months among patients not on insulin.

Patients in the study were limited to those who had been diagnosed with diabetes for at least a year and fewer than 2 years and were on medication for treatment of diabetes. The researchers accessed the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to find patients with pancreatic cancer in the U.S. between 2007 and 2011.

When they narrowed that group down to those being treated for diabetes, they ended up with 1,916 patients for the study. Of that group, 1,098 were on metformin; 818 patient were not taking metformin.

“The mainstay of treatment in pancreatic cancer remains as radiation and chemotherapy,” she said.

Sarcopenia Survival

While being on statins and/or metformin may give patients diagnosed with pancreatic cancer a leg up on survival, the patients' physical condition also plays a major role in their survival, said Kajal Patel, BS, a second year medical student at Drexel University, Philadelphia.

Patients diagnosed with sarcopenia tend to have a reduced overall survival, mainly because they are less likely to be candidates for potentially curative surgery for pancreatic cancer, she reported in a poster presentation.

“The patients had a lower performance status that would have precluded surgery,” she told Oncology Times. “Absence of sarcopenia may be useful in identifying better prognosis patients.”

“Clearly, performance status and sarcopenia are related,” said co-author Joshua Meyer, MD, Assistant Professor of Radiation Oncology at Fox Chase Cancer Center, Philadelphia. “It could be that sarcopenia is a marker for micrometastatic disease that we just can't detect.

“If the patients are not fit for surgery, it makes sense that they would not have surgery. It is a very aggressive and morbid surgery, even in patients with good performance status.”

In the study, Patel identified 86 patients who met the inclusion criteria—were either borderline resectable patients or eligible for chemoradiation. The median follow-up for these patients was 14 months. Their median age was 70. She said 29 patients were diagnosed with sarcopenia—about 33.7 percent of the total group.

The one-year overall survival was 47.9 percent of the patients who were diagnosed with sarcopenia and 70.7 percent for patients without the skeletal muscle-wasting disease (P=0.047). That significant difference, however, disappeared when multivariate analyses were performed (P-0.289), the researchers reported.

Surgical resection was associated with cancer-specific survival benefit (P<0.001). Surgery was also associated with overall survival (P<0.001).

Pancreatic Cancer Solutions

In commenting on the studies, James D'Olimpio, MD, Medical Oncologist and Hematologist at the Northwell Health Cancer Institute, Lake Success, N.Y., noted, “These linked studies on patients with pancreatic cancer appear to have increased our practical information that can be useful in the clinic, and also confirm clinical observations by many oncologists.

“Patients' overall robust physical condition often predicts a better outcome, and this is now confirmed with the measurement of the impact of sarcopenia,” he said.

“In addition, it appears that metformin, a commonly used drug to lower blood sugar, may have a protective or beneficial effect on patients who are diabetic who have pancreatic cancer even when their blood sugars are controlled with other means, and may even be considered for those who are not diabetic in the future.

“And lastly, another common drug, a statin used to lower cholesterol, may have an impact on improving outcomes in patients with pancreatic cancer independent of a cholesterol lowering effect,” D'Olimpo suggested.

“In essence , it would appear that relatively simple decisions on improving patient's functional status, either continuing or adding metformin to a pre-existing diabetic regimen, and continuing statins in these patients appear to have some merit moving forward with the management of this devastating disease, and deserve further study,” he said.

Ed Susman is a contributing writer.

Wolters Kluwer Health, Inc. All rights reserved.
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