The Trouble with Taxol

The Moss Reports Newsletter (10/28/07)


PART ONE In a major setback for the advocates of adjuvant chemotherapy, research published in the New England Journal of Medicine has shown that the widely used drug Taxol (paclitaxel) does not benefit women with the most common form of breast cancer.

It is estimated that more than 20,000 US women per year are given Taxol after surgery, in an attempt to prevent a recurrence. This represents about half of all the women who get chemotherapy for breast cancer.

Taxol is frequently given in the so-called ACT regimen, which is a combination of three drugs given in sequence, at varying intervals. Typically, Adriamycin (doxorubicin) is given along with Cytoxan (cyclophosphamide) for four cycles. This is then followed by four cycles of Taxol (paclitaxel). The disturbing new analysis comes from the Cancer and Leukemia Group B (CALGB), a research and clinical trials consortium that includes Larry Norton, MD, Eric Winer, MD, and other eminent doctors at Memorial Sloan-Kettering Cancer Center and elsewhere.

The study used modern genetic tools to reanalyze data that was gathered in a clinical trial in the 1990s. About 175,000 women are diagnosed with breast cancer in the US each year. Of these, about one quarter are diagnosed with locally advanced disease – i.e., cancer that has already spread to the nearby lymph nodes, but not yet to distant organs.

Many readers will remember the near-hysteria that accompanied approval of this so-called “natural” agent in the 1990s. (Taxol is a semi-synthetic derivative of the bark of Taxus baccata, the Pacific yew tree.) The Food and Drug Administration (FDA) approved the drug in 1999 as an adjuvant treatment for breast cancer – sequentially following the use of Adriamycin. In the CALGB study, 3,000 women with locally advanced breast cancer were given the ACT regimen. While Taxol only benefited a minority of patients, its adverse effects were experienced by the majority of patients. The adverse reactions to Taxol are well known.

These are tabulated in the drug’s prescribing information and can be readily found at the FDA Web site, www.fda.

Here are a few statistics, derived from a study of the single-use of Taxol in 812 breast cancer patients.

Neutropenia – 52 to 90 percent of patients, depending on the dose.

Leukopenia – 17 to 90 percent

Anemia – 16 to 78 percent

Infections – 30 percent

Hypersensitivity reactions – 41 percent

Hypotension – 12 percent

Abnormal ECGs – 23 percent

Peripheral neuropathy, any symptoms – 60 percent

Myalgia/arthralgia – 60 percent

Nausea and vomiting – 52 percent

Alopecia (hair loss) – 87 percent Injection site reactions – 13 percent

Some of these problems, such as numbness and tingling in the hands and feet, persist for months and years following Taxol treatment. The CALGB authors retrieved frozen tissue samples from 1,500 of the original trial participants and then ran tests to identify the genetic type of their tumor tissue. They found big differences between the patients who responded to Taxol and those who did not.

In women who had tumors that were estrogen-receptor positive, and in women whose tumors did not over-express the HER2 gene – and about 80 percent of all women who get breast cancer fall into this category – Taxol added no benefit at all to their survival odds.

However, in women whose tumors over-expressed the HER2 gene, and in those whose tumors were estrogen-receptor negative, Taxol added modestly to the odds of survival. According to the results of this new study, Taxol therefore stands to benefit around 20 percent of all women with breast cancer.

Ralph Moss

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