A two-step drug therapy that selectively targets tumors may hold promise for some patients with advanced cancers, according to results of a clinical trial directed by researchers in London.
Scientists at the University College Londons Cancer Institute and the Royal Free Hospital used a technique called antibody-directed enzyme prodrug therapy (ADEPT) in 43 patients with previously treated, advanced colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, or pancreatic cancers, or cancers of unknown primary site. The patients received one, two or three ADEPT treatments over a period of two to 10 days, at dosages ranging from 37 mg/m2 to 3,226 mg/m2.
We found clinically significant responses in 44 percent of patients, said senior author Richard H. Begent, M.D., professor of oncology at the University College Londons Cancer Institute. These results support the case for conducting a randomized phase II clinical trial.
ADEPT is a two-step treatment for cancer that uses an antibody to carry an enzyme directly to the cancer cells. First, an antibody is given with an enzyme attached. Next, a prodrug (inactive anti-cancer drug) is administered. When the prodrug comes in contact with the enzyme, the resulting chemical reaction activates the anti-cancer drug, which is then able to destroy cancer cells while sparing nearby healthy tissue.
In this trial, the researchers gave patients an intravenous dose of MFECP1, a recombinant fusion protein consisting of a fragment of an antibody raised against the substance carcinoembryonic antigen (CEA), which is produced by the cancer, and carboxypeptidase
G2 (CPG2), an enzyme that activates a prodrug. Then, researchers gave patients an intravenous bis-iodo phenol mustard prodrug which is activated by the enzyme within the cancer.
Anti-enzyme antibody developed in 40 percent of patients having a singl
|Contact: Staci Vernick Goldberg|
American Association for Cancer Research