The results also impressed PharmaMar enough for the company to seek approval this year to market the drug in Europe, according to Immacuada Abella, the company’s director of marketing and sales. In other Phase II trials, including those done in Europe, 10-15 percent of patients experienced tumor shrinkage, and the disease stopped progressing in another 30 percent.Ĭhabner refers to the results as “modest, but encouraging.” He adds that “ET-743 can be given with relative safety to people without liver disease, and these people have a reasonably good overall survival rate.” Of the first 101 people with advanced soft-tissue cancers who took the drug, tumor shrinkage occurred in 20 and tumor growth stopped in another 31. At the Harvard hospitals, these trials were led by George Demetri of the Dana-Farber Cancer Institute and David Ryan of Massacusetts General. PharmaMar moved on to Phase II tests, conducted to determine how well a drug works, in 1999. However, this side effect “turned out to be reversible and manageable with repeated treatments,” Chabner says. In the beginning, ET-743 appeared to cause liver problems. Five tests for safety, so-called Phase I trials, were done on 188 patients in the United Kingdom, France, and the United States. PharmaMar licensed the drug in 1994 and began testing it in humans two years later. Kenneth Rinehart, a chemist at the University of Illinois, discovered ET-743 (ecteinascidin) in squirts he collected in the West Indies in the late 1980s. Sea squirts are vase-shaped sacs of tough tissue that filter food particles from the water with the help of two siphonlike openings at the top. (Photo courtesy of PharmaMar) Tumors shrunk Sea squirts are being collected from ocean bottoms and raised on farms to produce a substance one-half ounce of which can treat 1,000 cancer patients. According to Corey, a mere 11 pounds of the drug would satisfy world demand for about a year.

But it is so incredibly powerful, only 0.05 ounce is enough to treat 100 patients. PharmaMar says that a harvest of about 95,000 pounds of sea squirts yields a scant 3 ounces of the drug. He called it “the most complex molecule ever made on a commercial scale.”

Corey, Sheldon Emery Professor of Chemistry at Harvard, managed to make the drug synthetically. “Tests show that the drug has been active enough to expand these trials,” says Bruce Chabner, a professor of medicine at Harvard Medical School. In the United States, researchers at three Harvard University-affiliated hospitals – Massachusetts General Hospital, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital – have been testing the drug on patients with breast, ovarian, and prostate cancer. If received, PharmaMar expects to begin selling the drug in Europe by the end of this year for treatment of soft-tissue sarcomas, cancers affecting blood vessels, muscles, tendons, and other connective tissues including those that hold internal organs in place. Tests on hundreds of patients in Europe have been encouraging enough for the company to apply for approval to market the drug, which they call ET-743. In addition to collecting the squirt, known as Ecteinascidia turbinate, from sea bottoms around the world, a Spanish company, PharmaMar, has established an underwater farm on which the tubelike creatures are being raised. Trials conducted in the United States and Europe show that the compound has promising activity against connective tissue, breast, ovary, and prostate tumors. (Staff photo by Kris Snibbe)Ī powerful cancer drug found in the tissues of sea squirts is being tested on a variety of cancers. The drug is being given to patients with breast, ovarian, prostate, and connective tissue tumors.

Professor of Medicine Bruce Chabner is helping to organize tests of a powerful new cancer drug extracted from sea squirts.

Seashore drugs