Forbes (KC) 13-Apr-08

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A new drug duo might help prevent colorectal cancer, and the powerful new cancer drug Sutent may slow the progression of liver cancer.

New Treatments Help Fight Liver, Colon Cancer

A new drug duo might help prevent colorectal cancer, and the powerful new cancer drug Sutent may slow the progression of liver cancer. So conclude two studies presented Monday at the American Association for Cancer Research annual meeting in San Diego.

In the first report, researchers found that a two-drug regimen made up of low doses of difluoromethylornithine (DFMO) plus sulindac, a non-steroidal anti-inflammatory drug (NSAID), cut the risk of colorectal adenomas by up to 95 percent. Colorectal adenomas are an early sign of colon cancer.

"We really think we are on track to develop a medical means to prevent colon cancer," lead researcher Dr. Frank L. Meyskens, a professor of medicine at the University of California, Irving, told reporters during a Monday afternoon teleconference.

Meyskens believes the drug combo could be used for people at high risk for colon cancer to prevent the disease from developing. It could also be used by those who have already had colon cancer, to help prevent its return, he said.

In the phase III trial, researchers studied 375 people with a history of colorectal polyps. They randomly assigned patients to a combination of DMFO and sulindac or placebo. Patients were followed for three years.

Patients taking the combination of drugs saw a 70 percent reduction in the risk of a new adenoma compared with patients receiving placebo.

For people who had advanced adenomas, the risk of developing new adenomas was reduced by 92 percent among those on the drug combination, Meyskens said.

Moreover, patients taking the drug combination who had had large adenomas saw a 90 percent reduction in their risk of developing new adenomas compared with patients taking placebo.

"The real home run was that we had a 95 percent decrease in new adenomas in those patients who had multiple adenomas," Meyskens said. "So, 17 patients in the placebo group had more than one adenoma, compared with only one patient in the treatment group," he said.

The rate of risk reduction was so high that the trial's Data Safety and Monitoring Board stopped the trial early so that everyone could benefit, the researchers noted. In addition, there was no difference between people getting the medications and placebo in terms of side effects requiring hospitalization, gastrointestinal side effects, cardiovascular side effects or temporary hearing loss, a rare side effect of DMFO.

In the second study, the researchers showed that sunitinib (Sutent) appears effective in slowing tumor growth and cutting the risk of metastases in patients with hepatocellular liver cancer, researchers report.

Sutent, a member of a family of cancer drugs that also includes Gleevec (imatinib), has proven effective against kidney cancer and a type of malignancy called gastrointestinal stromal tumors. Recent studies have also linked Sutent to higher heart risks, so experts say cancer patients and their doctors must weigh its risks and benefits.

The new study focused on hepatocellular liver cancer. "Hepatocellular cancer is a very challenging cancer to deal with," lead researcher Dr. Andrew Zhu, an assistant professor of medicine at Harvard Medical School said during the Monday afternoon teleconference. "It is a very common cancer worldwide, and it is the third leading cause of cancer mortality," he said. "The cancer most likely results from having had a hepatitis B infection."

The prognosis associated with this cancer is very poor, Zhu noted. "The average survival is six to eight months," he said.

In the study, 34 patients with advanced liver cancer were given Sutent daily for four weeks with two weeks off before the next round of treatment. Sutent works by targeting receptors in cancer cells called VEGFR2, c-Kit and FLT3. These receptors are also present in normal cells.

The drug appears to work by controlling the growth of blood vessels, which is how this type of liver cancer is able to spread so rapidly.

At 12 weeks, one patient had a partial response and 17 saw their disease stabilize. Progression-free survival lasted an average of four months, and overall survival was 10 months, the researchers report.

"Even though the response rate to make the tumor smaller was observed in only one patient, 50 percent of the patients had stable disease and are doing well," Zhu said. "Sunitinib can be safely given, with close monitoring, to the majority of these patients," he said.

The treatment was well-tolerated, and there were low rates of all blood disorders, the researchers report. Because Sutent has been associated with increased risk of heart problems, all patients taking Sutent -- but especially those who have risks for heart disease -- need careful monitoring and treatment for high blood pressure and other signs of heart problems.

In a third report, researchers from the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia found that blood pressure-lowering drugs called angiotensin receptor blockers appear to retard pancreatic cancer cell growth and cause malignant cells to die.

This type of drug is able to inhibit the function of the hormone angiotensin II in the pancreas. The same receptor is found in pancreatic cancer cells. In laboratory experiments, the researchers found that the drug was able to block the production of a growth factor called VEGF, which helps spur the growth of tumor blood vessels.

"This is really exciting because the role of this receptor has never been known," lead researcher Dr. Hwyda Arafat said in a prepared statement. "It's never been connected to cell division or apoptosis. We're also now further exploring the mechanisms involved. The exciting thing is that this receptor already has so many available pharmaceutical blockers on the market." Ultimately, the group hopes to be able to test these agents in human trials, she said.

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