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Taxol

The pinnacle of NCI’s success in its natural-products screening program is paclitaxel (now better known by its trade name, Taxol), a chemotherapy drug derived from the bark of the Pacific yew (Taxus brevifolia) and the needles of other yew species. (The trade name Taxol is owned by Bristol-Myers Squibb Company, makers of the drug.)

The Pacific yew is a small evergreen tree found scattered throughout forests from southeastern Alaska to northern California and eastward to Montana and Idaho. It is rarely cultivated. Other species in the genus Taxus, including English yew (T. baccata) and Japanese yew (T. cuspidata), are widely grown as ornamentals. The foliage, bark, and seeds of yews are poisonous.

In 1962, the U.S. Department of Agriculture collected Pacific yew bark for NCI because paclitaxel, like many other compounds, had shown activity against several experimental leukemia cell models. In 1975, observation of strong activity in the B16 melanoma system created more interest in the compound. Further tests showed significant experimental activity in a number of human tumors, including one form of breast cancer. A breakthrough occurred in 1979 when researchers at the Albert Einstein Institute in New York discovered how the compound prevents the reproduction of cancer cells. By 1980, toxicological studies had begun, and formulation studies were completed.

In 1983, the U.S. Food and Drug Administration (FDA) granted approval for the first phase of clinical trials to study paclitaxel’s safety and evaluate doses and regimes. Progress was slow because of severe shortages in the supply of yew bark. (The Pacific yew is a slow-growing tree often found in old-growth forests, and harvesting the tree’s bark destroys it.) Preliminary reports showing a response rate of 30 percent in ovarian cancer studies exacerbated the supply problem by increasing the demand for Taxol for clinical trials. In 1991 and 1992, studies showed that patients with metastatic breast cancer (responsible for the death of 40,000 women per year in the United States) responded positively to the drug as did patients with advanced lung cancer, cancer of the head and neck, melanoma, and lymphomas.

In 1993, Taxol was approved as a therapeutic agent for ovarian cancer resistant to other treatments and in 1994, for certain forms of breast cancer.

The current FDA approval of Taxol for treatment of ovarian cancer applies only after other therapies have failed, but increasingly physicians are using it for first-line therapy. Some 55 percent of ovarian cancer patients in the United States are currently receiving Taxol as part of their primary therapy. In May 1995, a clinical study by William McGuire, of Emory University’s Cancer Center, reported that about 73 percent of nearly 400 women responded favorably to treatment with a combination of Taxol and another chemotherapy agent, cisplatin, and recommended that this combination become the standard of therapy worldwide for women with ovarian cancer.

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