Counting number of endothelial cells in blood may predict cancer treatment's effectiveness

May 15 2005

Counting the amount of a type of normal cell circulating in the blood of people with cancer could predict whether a tumor progresses or responds to therapy, a new study led by the University of Michigan Comprehensive Cancer Center has found. The finding could give doctors an early indication of whether a treatment will be successful, sparing patients months of an ineffective therapy.

Researchers looked at the number of endothelial cells - normal cells lining the blood vessels - that were circulating in the blood of people with sarcoma. Previous studies have shown that higher levels of circulating endothelial cells are found in people with cancer compared to people who are cancer-free. In this study, researchers found patients whose cancer grew after two months of treatment had high levels of circulating endothelial cells before beginning therapy, while patients whose cancer remained stable had low levels of these cells.

"This test can be used to predict the patient's outcome and survival. In addition, there are a number of drugs available in the clinic, and it may be possible to use this test to monitor the effectiveness of a drug in an individual patient," says Laurence Baker, D.O., professor of internal medicine and pharmacology at the University of Michigan Medical School. Baker will present the study results Saturday, May 14, at the American Society of Clinical Oncology annual meeting in Orlando, Fla.

Circulating endothelial cells are the target of new anti-angiogenesis drugs, which are designed to inhibit the growth of blood vessels that feed tumors. Angiogenesis, the natural process of blood vessel formation, is believed to contribute to the growth and development of cancer cells.

In this multicenter trial, researchers took blood samples from 88 people with advanced sarcoma, a cancer of the soft tissues, and analyzed it to determine the number of endothelial cells circulating in the blood. Angiogenesis inhibitors target these cells, so a change in the number of circulating endothelial cells would suggest a change in tumor status.

"Because the endothelial cell is the target of these anti-angiogenesis drugs, you might be able to very quickly determine if therapy is working," Baker says. Traditionally, patients undergo X-rays and other imaging scans to see if the tumors have disappeared or shrunk.

Study participants were given a new anti-angiogenic drug called ABT-510. As part of a phase II trial, patients with advanced soft tissue sarcoma were randomly assigned to one of two doses of ABT-510. They were assessed every eight weeks to determine whether the tumor was responding to the treatment. The study looked at people with advanced sarcoma that had metastasized, or spread to other parts of the body. Survival rates for this stage of sarcoma are very low: about 10 percent to 15 percent are alive after five years.

In more than one-third of patients taking ABT-510, the cancer had not progressed six months after therapy. With standard drugs, only 14 percent of patients do not see their cancer progress by six months.

ABT-510, an angiogenesis inhibitor in development at Abbott Laboratories, is believed to work by slowing or stopping the growth of blood vessels, thereby choking off a tumor's blood supply. These types of drugs target endothelial cells, causing them to die and preventing new blood vessels from being formed.

In this trial, circulating endothelial cell levels in the study participant's blood were evaluated at the start of the trial, one month in and every two months thereafter. Researchers identified circulating endothelial cells through flow cytometry, an analysis method that separates cells by energy, and by stains that attract to specific types of cells.

Researchers found that patients with low circulating endothelial cell counts, defined as fewer than 15 per sample of blood, remained on the therapy longer than people who had more than 15 circulating endothelial cells per sample at the start of treatment or a month into treatment. Patients were allowed to remain on the therapy until their tumor grew by 50 percent.

The findings suggest doctors may be able to tailor treatment based on the likelihood of response, potentially switching patients from treatments that are not working for them and sparing them months of unnecessary side effects.

ABT-510 is among several angiogenesis inhibitors being tested in different types of cancer, including sarcoma, breast cancer, lung cancer and colon cancer.

In addition to Baker, study authors are George Demetri of the Dana Farber Cancer Institute; David Mendelson and Michael Lobell, both from the University of Arizona; Eric Rowinsky of the Cancer Therapy and Research Center in San Antonio, Texas; and Evelyn McKeegan, Raymond Knight, Dawn Carlson and Paul Cernohous, all from Abbott Laboratories.