Scot Remick, MD, director of developmental therapeutics at the Ireland Cancer Center, offered conclusive evidence that the anti-tumor vascular targeting agent, Combretastatin A4 Prodrug (CA4P), successfully reduces blood flow that feeds malignant tumors. Essentially, the drug deprives a tumor of the nutrients it needs to grow. Combretastatin A4P is the first vascular targeting drug to be tested in a human trial in the U.S. Evidence was presented through complex MRI (magnetic resonance imaging) scans of blood flow in patients being treated with Combretastatin A4P. Significant reduction in the tumor blood flow was seen 4 to 6 hours following infusion of the drug.
“We were able to demonstrate the ability to reduce tumor blood supply at tolerable dosage levels, without traditional cytotoxic side effects,” said Dr. Remick. “In short, we were able to demonstrate the concept of tumor vasculature targeting.” Unlike anti-angiogenesis drugs that inhibit the formation of new blood vessels in a tumor, vascular targeting agents attack blood vessels that already exist to support the primary tumor mass.
A total of 25 patients participated in the Ireland Cancer Center trial at The Research Institute of University Hospitals of Cleveland. Some highlights include:
· One 55-year old man with anaplastic thyroid carcinoma who had a “pathological complete remission” after undergoing Combretastatin A4P treatment and remains disease-free more than two years later.
· Two other patients experienced “prolonged periods of freedom from progression of their disease.”
· A patient with colon cancer remained stable for 19 months, while another with medullary thyroid cancer remained stable for 12 months.
Other Phase I trials at the University of Pennsylvania in Philadephia, Pa., and in the United Kingdom showed similar promising results. In those studies, dose-limiting toxicity was tumor pain or reversible ataxia (unsteady gait); in Cleveland, dose-limiting toxicity included pulmonary side effects and acute coronary syndrome.
Combretastatin A4P is derived from the African bush willow Combretum caffrum. The drug may also be tested in combination with other chemotherapy and radiation to see if it enhances the effectiveness of traditional cancer treatments. The drug was developed by OXiGENE, Inc., an international biopharmaceutical company.