Vitamin K and Sorafenib Combination Demonstrated Anti-Tumor Effects in Pancreas Cancer and Hepatocellular Carcinoma
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.
Media Only Contact:
Emily Shafer
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 4/22/2009