M. D. Anderson Researchers Present Promising New Drug Results

Early results from the Phase I trial of Endostatin at The University of Texas M. D. Anderson Cancer Center, sponsored by the National Cancer Institute under a Cooperative Research and Development Agreement, show the drug did no harm to patients and indicate some encouraging results.

Endostatin is one of several so-called "anti-angiogenesis" drugs that work to kill tumors by cutting off their blood supply.

Investigators remain cautious in their remarks about the drug that has generated national publicity and great public interest.

"It is important to note that the drug was well tolerated by the patients,"said Dr. James Abbruzzese, chairman of the Department of Gastrointestinal Medical Oncology and the director of the grant under which the Endostatin trial was conducted.

Preliminary study results were presented recently in Amsterdam at the 11th annual "Symposium on New Drugs in Cancer Therapies," sponsored by the National Cancer Institute, European Organization for Research and the Treatment of Cancer, and American Association of Cancer Research. Investigators show that patients tolerated the drug well, with few toxic side effects.

The Phase I clinical trial seeks to determine the safety of Endostatin and to determine the dose at which it can be given effectively. To best determine this optimal biologic dose, the study analyzed a large panel of surrogate tissue and radiologic endpoints on every patient.

According to Dr. Roy Herbst, principal investigator of the M. D. Anderson study, patients were given graduated doses of Endostatin daily for 20 minutes with intravenous infusion. The trial continues at this time with limited enrollment and is expected to conclude within the next few months.

Preliminary results of the M. D. Anderson trial describe the experience of 20 patients with varied diagnoses which include breast cancer, melanoma, head and neck cancer, colon cancer, renal cell carcinoma and sarcoma. Fifteen men and five women were enrolled in the trial, with ages ranging from 29 to 78 years old.

Of the 20 patients, one patient had a greater than 50 percent reduction in tumor volume and a second patient had stable disease for approximately one year. The other patients have not experienced any major clinical benefits.

Three more M. D. Anderson patients will be added to the NCI-sponsored

Phase I trial by the end of the year. The first patient started the trial in November 1999.

All patients were selected for the study from among current M. D. Anderson patients. Selection of patients was based upon ease of tumor biopsy, individual performance status, disease site and order of evaluation. All the patients had failed previous standard treatments or had no standard therapy for their disease. Patients were required to have frequent tumor biopsies to study the biological effects of the drug, so they remained in Houston for the length of the trial.

"Frequent blood samples were drawn and analyzed to monitor for Endostatin concentration," said Dr. Hai Tran, director of the Clinical and Translational Resource Center at M. D. Anderson and Endostatin investigator. "We are encouraged that we have reached the targeted blood levels for anti-angiogenic activities as seen in the pre-clinical models."

During the trial, in addition to the regular biopsies, patients had regular Computerized Tomography (CT) scans and Positron Emission Tomography (PET) scans.

All three diagnostic tests, plus ongoing pharmacology tests and physical examinations, helped to determine the optimal biological dose of the drug through measurement of blood flow and metabolic activity within tumors, and monitor patients' reactions to the drug.

"While the results are still preliminary for the Phase I trial, the drug appears to be safe to give patients. We know we are achieving blood levels which were targeted at the beginning of the study. This has been a definitive success in this trial. We are working diligently to determine an optimal biologic dose through a series of surrogate studies which include non-invasive imaging and tumor biopsies," said Dr. Herbst, who is assistant professor in thoracic/head and neck medical oncology and assistant professor of cancer biology.

"This is a good example of how a large, multidisciplinary team of individuals backed by the clinical and academic resources of

M. D. Anderson has been able to quickly translate a laboratory finding to the clinic. While our primary goal has been to make these new agents available to our patients, the rigorous clinical and scientific assessments associated with this study have enabled us to more fully evaluate the anti-angiogenic activity of Endostatin," said Dr. Herbst.

"We hope this new paradigm will speed the development process of Endostatin and other anti-angiogenic agents in the future, to bring them more quickly and effectively to common clinical practice," he added.

For more information about available cancer treatment options and clinical trials for patients, call the M. D. Anderson Information Line at 1-800-392-1611 or visit the web site at www.mdanderson.org.

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©2006 Texas Medical Center

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