Many patients had a response to the radiation and drug treatment, meaning their disease either temporarily stopped growing or regressed somewhat. "The majority of patients experienced some regression of their tumor. This is sometimes seen with radiation, but we can't rule out that this is due to Angiostatin or Angiostatin and radiation," says Dr. Dicker, who is also director of the Division of Experimental Radiation Oncology at Jefferson Medical College. Dr. Dicker presents the team's results May 20 at the American Society of Clinical Oncology meeting in Orlando.
The Jefferson team previously presented evidence last month at the American Association for Cancer Research meeting in San Francisco showing Angiostatin enhances the effects of radiation and "delays tumor regrowth" in the laboratory. They have seen little evidence to date of toxicity from the drug. "We think Angiostatin is very safe both preclinically and clinically," Dr. Dicker says. "We haven't seen any toxicity other than that you would expect with radiation alone. It's an important study that will lead to future trials of combination therapy with Angiostatin." In the study, patients received recombinant Angiostatin - an angiogenesis inhibitor drug candidate being developed by EntreMed, Inc., a Rockville, Md.-based biotechnology company - intravenously five times weekly 30 minutes prior to radiotherapy during a five-to-seven week period. The type and location of the patient's tumor determined radiation doses. Some patients had chemotherapy prior to the study. According to Dr. Dicker, in another clinical trial, Angiostatin is currently being administered subcutaneously - under the skin - similar to the way diabetics give themselves insulin shots.
The Angiostatin-radiation trial was one of two Phase I trials involving Angiostatin conducted simultaneously at Thomas Jefferson University Hospital and Jefferson's Kimmel Cancer Center - the first trials of Angiostatin in the United States. The other trial found that giving Angiostatin alone to patients with advanced cancer who had failed prior chemotherapy was safe and had few side effects. Phase I trials test for safety and to determine how the body handles the drug - not necessarily to measure effectiveness. Angiostatin is a protein and a natural tumor inhibitor discovered several years ago in mice in the laboratory of Harvard scientist and surgeon M. Judah Folkman, M.D., and now being developed by EntreMed. It works by blocking the formation of blood vessels, based on the theory that cancers cannot grow or spread without a blood supply - a process known as angiogenesis. Some researchers believe that Angiostatin and other angiogenesis inhibitors will expand the armamentarium of drugs that will halt cancer growth, enabling patients to live with their disease as cancer becomes a chronic illness.
Editors: This information is embargoed for release on May 20 at 12 p.m. at the annual meeting of the American Society of Clinical Oncology in Orlando. (Abstract no. 23)