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Extra Drug Improves Rectal Cancer Treatment
Date:4/15/2008

And contraceptive drug helps kill cervical cancer cells missed by chemotherapy

TUESDAY, April 15 (HealthDay News) -- Adding the cancer drug Avastin to radiation and chemotherapy improves results for patients with rectal cancer.

And adding the contraceptive drug mifepristone (RU-486, the so-called abortion pill) to chemotherapy kills ovarian cancer cells that escaped cisplatin treatment.

Those are the conclusions of two reports on new trends in cancer drugs presented Tuesday at the American Association for Cancer Research annual meeting, in San Diego.

In the first study, researchers found that adding Avastin to chemotherapy and radiation improved three-year, disease-free survival by 91 percent among patients with rectal cancer.

"Avastin is an antibody against a potent angiogenic molecule known as vascular endothelial growth factor (VEGF) and has been approved to treat several types of cancers," Rakesh K. Jain, director of the Edwin L. Steele Laboratory for Tumor Biology at Massachusetts General Hospital, said during a teleconference. In essence, VEGF promotes the growth of blood vessels in cancer tumors, he said.

According to the U.S. National Cancer Institute, there are more than 40,000 new cases of rectal cancer diagnosed each year in the United States.

The goal of Jain's team's research was to find ways to make standard chemotherapy more effective. For the study, 25 patients with rectal cancer were treated with Avastin, along with chemotherapy and external beam radiation and surgery. The addition of Avastin increased the density of blood vessels in the tumor and repaired tumor vessels damaged by chemotherapy or radiation, he said.

"Avastin leads to vessel normalization, it repairs vessels," Jain said. "By repairing the vessels, it makes the tumor better-nourished so the drugs can get there and work better," he said. "That's a very counterintuitive finding."

Avastin alone, or in combination with other treatments, increased levels of the factors VEGF, PlGF and SDF1 alpha, the researchers reported. Patients with higher levels of VEGF and PlGF after Avastin responded better to chemotherapy and radiation, Jain said.

The increase in SDF1 alpha suggests that this factor could be a new drug target to extend the life of patients after other therapies have failed, Jain said. "This is a new drug candidate," he said.

Among the patients receiving Avastin, local control of their disease reached 100 percent, Jain said. "Three-year, progression-free survival was 91 percent," he said.

Jain cautioned, however, that these results were very preliminary and needed to be confirmed.

In the second study, researchers found that using mifepristone along with the chemotherapy drug cisplatin might improve success in treating ovarian cancer.

"Mifepristone, which was initially created for contraceptive purposes, has a therapeutic effect against ovarian cancers that remained after standard cisplatin therapy," lead researcher Dr. Carlos M. Telleria, an assistant professor of medicine at the University of South Dakota Sanford School of Medicine, said during Tuesday's teleconference.

One of the main problems in treating ovarian cancer is that the usual treatment with the chemotherapy drug cisplatin doesn't kill all the cancer cells. This allows the cells to reform into colonies and the cancer to continue to grow.

"We show for the first time that mifepristone is effective in preventing the re-growth of ovarian cancer cells that survive standard cisplatin chemotherapy," Telleria said.

There are more than 20,000 women diagnosed with ovarian cancer every year in the United States, and more than 15,000 women die from the disease annually, Telleria noted.

In the study, the researchers exposed ovarian cancer cells to cisplatin. Although cisplatin killed the majority of the cells, there were cells that escaped and regrouped as cancer. This happened all three times the cells were treated with cisplatin over 36 days.

However, when cells were treated with cisplatin and then exposed to mifepristone, none of the cancer cells survived, the researchers found.

"This study suggests that mifepristone has the potential to improve the success of the standard platinum drugs in the treatment of ovarian cancer," Telleria said.

More information

For more on cancer, visit the American Cancer Society.



SOURCES: April 15, 2008, teleconference with Rakesh K. Jain, Ph.D., director, Edwin L. Steele Laboratory for Tumor Biology, Massachusetts General Hospital, Boston; Carlos M. Telleria, M.D., assistant professor of medicine, University of South Dakota Sanford School of Medicine, Vermillion; American Association for Cancer Research annual meeting, San Diego


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