New Source for Cancer Drug Found : Medicine: Researchers say they can now make taxol from the leaves and branches of yew trees instead of the bark. The finding means forests that are home to spotted owls would not be devastated.
Researchers said here Tuesday that they have cleared a crucial hurdle in the production of taxol, widely considered to be the most promising anti-cancer agent of the past 20 years.
The new drug, which has proven highly effective in treating ovarian, breast and lung cancers, is currently extracted only from the bark of old Pacific yew trees in forests of the northwestern United States, home of the endangered spotted owl. Environmentalists have feared that the effort to produce enough taxol to meet the needs of patients would devastate the forests and drive the spotted owl to extinction.
But U.S. and French researchers have devised a technique to produce taxol from a chemical that is present in high concentrations in the leaves of both the Pacific and European yew trees. This compound, called 10-deacetylbaccatin III, can be collected in adequate quantities from tree trimmings without damaging the trees themselves, researchers said at a meeting of the American Chemical Society.
Bristol Myers-Squibb Corp. is constructing a taxol-production facility that will use the leaves and branches, and it is making commercial agreements for collection of the material. The company expects to be producing commercial quantities of taxol by the spring of 1993, said Florida State University chemist Robert A. Holton, who developed the process by which 10-deacetylbaccatin is converted into taxol and whose work has been partially funded by the company.
These new processes “will end our dependence on the Pacific yew tree,” and the use of bark from it “should decline pretty sharply” over the next year, said medicinal chemist Matthew Suffness, program director for taxol at the National Cancer Institute in Bethesda, Md. “The spotted owl is safe,” he said.
At the same conference, French researchers also argued that American scientists should abandon their work on taxol and switch to a newer drug, called Taxotere, that they say is even more powerful than taxol. Taxotere is also made from the leaves of the European yew tree, but it is simpler to produce than taxol.
Suffness countered that it would be premature to make a hasty switch to Taxotere, but he noted that clinical trials of the French drug are also in progress in the United States. “What we really need is a head-to-head trial between the two drugs” to make a decision, he said.
Also at the meeting, chemist Paul Wender of Stanford University said that his team is very close to completing a total synthesis of taxol from pinene, a widely available, inexpensive compound that is the primary ingredient of turpentine. Although it now appears that a completely synthetic form of taxol may not be necessary, the work is expected to be valuable in producing analogs (chemically similar compounds) of taxol that might have even greater biological activity.
Cancer researchers are excited about taxol because it works by a different mechanism than other anti-cancer drugs and is effective against many tumors that have become resistant to conventional chemotherapeutic agents.
Recent clinical trials, Suffness noted, showed that taxol produced a beneficial response in 30% of ovarian cancers that were not responsive to any other form of treatment and in 50% of similar metastatic breast tumors.
But the treatment of one patient requires all the bark from three to six 100-year-old yew trees. In 1991, the United States harvested more than 100,000 trees for this purpose, and similar harvests had been expected over the next few years. Such wholesale harvesting has been highly criticized by environmentalists and has produced fears that insufficient quantities of the drug will be available in the future.
The compound was discovered in the leaves and branches of the European yew in 1984 by chemist Pierre Potier of the Centre National de la Recherche Scientifique in Gif-sur-Yvette, France. He also developed a procedure for converting it into Taxotere, now produced in commercial quantities in France by Rhone-Poulenc Rorer.
Potier said at the conference that Taxotere is more easily administered to patients than taxol, that it has fewer side effects and that it is as effective at half the dose. It can also be produced more easily.
