UW Comprehensive Cancer Center One Of Two Sites Nationwide Selected For Clinical Trial Of Cancer Drug

Article originally published in March, 1998

MADISON - The University of Wisconsin Comprehensive Cancer Center has been chosen as one of two sites in the nation to conduct human tests of endostatin, a promising potential cancer treatment that seems to work in part by disrupting the growth of blood vessels that nourish tumor cells.

The National Cancer Institute (NCI) notified the UWCCC early this afternoon of its participation.

"We are honored and very excited to be taking part in these trials," said UWCCC Director Dr. John Niederhuber. "This is an important opportunity to answer some key questions about a very interesting compound."

Endostatin's potential value as a cancer treatment received worldwide attention after a May 1998 New York Times article described early results in mice in the laboratory of Dr. Judah Folkman of Harvard Medical School. In May 1998, the NCI called animal studies on the compound "encouraging" and later announced it would entertain applications from research organizations to conduct tests in humans.

In animal studies, endostatin inhibited the growth of already existing tumors and caused some to shrink to microscopic lesions. When researchers examined those tiny lesions, they found the endostatin had blocked the growth of blood vessels that nourished the tumors.

Researchers also conducted tests in which mice were given endostatin until their tumors shrank, at which time the treatment was stopped. Treatment resumed when the tumors began to grow back. In each case, the tumors in mice became smaller when endostatin was given. Significantly, the tumors did not develop resistance to endostatin even after six cycles of treatment.

The trials at UW will be "Phase 1" tests in which researchers will try to discover the maximum dose patients can tolerate without undue toxicity. Initially, three to six patients will receive small doses of the drug and will be carefully monitored for toxic effects. Additional patients will then receive graduated doses of the drug. All patients will be carefully monitored through a variety of complex tests.

"The research team will recruit patients with solid tumors that have failed to respond to treatment," said principal investigator Dr. George Wilding, director of the UWCCC experimental therapeutics and professor of medicine at UW Medical School. Patients with renal cell carcinoma, mesothelioma, breast cancer and melanoma may be particularly suited to the trials because such tumors typically have a large number of blood vessels, the target of the drug.

Dr. Joan Schiller, UW Medical School professor of medicine, and Dr. James Thomas, assistant professor of medicine, will co-chair the study. Both are medical oncologists practicing at UW Hospital and Clinics and members of the experimental therapeutics program. Other collaborators include Kendra Tutsch of the UWCCC analytical lab; Dr. Robert Auerbach of the zoology department; Amy Harms of the UW Biotechnology Center; Drs. Fred Lee, Fred Kelcz, Scott Perlman, James Zagzebski and Thomas Grist of the UW Medical School radiology department; and Richard Chapell of biostatistics.

Wilding said the time at which patients will be enrolled is not certain. The study will need to go through several review processes, including the university's, the NCI's and the UWCCC.