NEW YORK (Reuters Health) - People who have undergone surgery for pancreatic cancer and are classified as obese don”t live as long as those who are not obese, according to a new report.

Dr. Jason B. Fleming, from the University of Texas, Houston, and colleagues looked at the outcomes of 285 patients with pancreatic cancer who were all treated at the M. D. Anderson Cancer Center. Obesity was classified as a body mass index or BMI of 30 or more.

Cancer was 12 times more likely to be found to have spread to the lymph nodes in patients with BMIs of 35 of more, compared to those with lower BMIs, the investigators report in the Archives of Surgery.

For patients with a BMI higher than 35, average survival was 13.2 months, compared with 27.4 months for those with a BMI of less than 23.

The cancer recurred in 95% of patients with a BMI above 35, while those with lower BMIs had a recurrence rate of 61%, the researchers note.

The results, they conclude, “suggest that obesity is a host factor affecting tumor biology independent of the difficulties… involved in delivering oncologic care in obese patients.”

SOURCE: Archives of Surgery

A combination of sorafenib and vitamin K had an effect in vitro on both human pancreas cancer and hepatocellular carcinoma, according to researchers from the Kimmel Cancer Center at Jefferson. Data from the two studies were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #5470 and #5483)

Vitamin K1 or vitamin K2, plus sorafenib (Nexavar) each have shown activity against the growth of human cancer cells by inhibiting the extracellular signal-regulated kinase (ERK) pathway according to Brian Carr, M.D., Ph.D., a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University. ERK plays a major role in cell growth of cancers.

Although sorafenib has demonstrated success at extending survival in patients with hepatocellular carcinoma (HCC, or primary liver cancer), hand-foot syndrome is a common adverse effect that affects approximately 20 percent of patients who receive the drug. It typically manifests as painful sores on the soles of patients’ feet that can prevent the patients from walking, Dr. Carr said. Profound tiredness and weight loss is also seen in at least 30 percent of patients.

In the pancreas cancer study, Dr. Carr and his colleagues tested each K vitamin in combination with sorafenib in pancreatic cell lines. Each combination inhibited cell growth, induced cell death and decreased the expression of ERK. They found that when combining vitamin K and sorafenib, the sorafenib dose required for inhibiting cancer cell growth decreased by more than 50 percent. This dose was ineffective when used alone.

“So few agents have activity against pancreas cancer,” Dr. Carr said. “One of the attractions of the combination of sorafenib and vitamin K is that both of these agents are already approved for human use. K vitamins also have no known adult human toxicities, and appear to enhance the effects of sorafenib, thus requiring lower, less-toxic doses.”

In the second study, vitamin K1 also enhanced the effects of sorafenib in HCC. Sorafenib is FDA-approved for the treatment of HCC, which typically arises on a cirrhotic liver, which tolerates conventional chemotherapy poorly. The researchers previously had shown that vitamin K alone is a weak inhibitor of HCC growth. In this study, they found that the combination inhibits the growth of HCC, induces cell death and decreases the expression of ERK.

“Many patients need to discontinue treatment with sorafenib because of the debilitating side effects,” Dr. Carr said. “If we could lower the dose, more patients would be able to complete their treatment.”

These data also pave the way for potential studies to evaluate the combination of sorafenib and vitamin K as an HCC prevention strategy in patients who are at greater risk for developing the disease. This population includes patients with cirrhosis or patients who have previously had surgery for HCC. According to Dr. Carr, the recurrence rate for HCC after surgery is 40 percent.

Source: Thomas Jefferson University

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