Oct. 19, 2007 The breast cancer drugs called taxanes, which include Taxol (paclitaxel) and Taxotere (docetaxel), increase survival rates when used as part of chemotherapy following surgery for cancers that have not spread, according to a new review of the research.
The review, which compared chemotherapy regimes using taxanes with those that did not, comprised 12 studies including 21,191 women.
"For patients, this study confirms that including taxanes in an adjuvant chemotherapy regimen for early breast cancer will improve their chance of living longer and remaining free of breast cancer," said review coauthor, Anna Nowak, M.D. "It also provides reassurance that there are many different ways of giving a taxane and that the individual choice of regimen may not be critical."
Taxanes increased overall survival by 2.6 percent and survival with no recurrence of the cancer by 4.1 percent, when compared to regimens without taxanes, the reviewers found.
Although the data appear to show that docetaxel is slightly better, this type of analysis cannot compare one drug to another accurately. "This hypothesis would be better tested in a clinical trial directly comparing the two drugs. Such trials are being done," said Nowak, a medical oncologist at the University of Sydney in Australia.
The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Some researchers have argued that taxanes themselves are no better than other kinds of chemotherapy for breast cancer -- and that the results of previous trials just showed that more and longer chemotherapy in general was better.
"These have been past criticisms of some of the earlier taxane trials," Nowak said. "I think that hypothesis has been disproved by this study."
"It looks like taxanes are beneficial," said Kay Dickersin, Ph.D., director of the Center for Clinical Trials at Johns Hopkins School of Medicine. Dickersin, who was not involved with the review, said that the studies analyzed appeared to be of good quality, which strengthens the result.
"For physicians, the study also demonstrates that there are numerous effective regimens and that there is no clear message that taxanes must be given together with anthracyclines, or as an extra drug, or for a longer number of cycles. This allows physicians to tailor the regimen to the individual patient in terms of side effects, duration and convenience," Nowak said.
She added that there was no increase in secondary leukemia associated with these drugs, at least during the patient follow-up periods so far, which had been a concern.
The review did confirm that certain side effects were higher among those treated with taxanes, including neurotoxicity (in this case, numbness, tingling, and/or weakness in hands and feet due to damage to nerves) and febrile neutropenia -- an infection that results from low white blood cell counts, which can be fatal. "However it was encouraging to see no additional treatment-related deaths in the taxane group," Nowak said.
There were also lower rates of nausea among those treated with taxanes and the review found that some regimens of these drugs were less likely to be harmful to the heart.
The studies showed that replacing another kind of drug called an anthracycline with a taxane could reduce the risk of heart damage. "This will also help physicians to choose a safer regimen in women who may be at higher risk of this complication," Nowak said.
Breast cancer is the most common cancer among women, affecting more than 1 million worldwide each year and killing some 400,000 annually. One in eight American women will receive a breast cancer diagnosis over the course of a lifetime. Thirty percent of those diagnosed will die from it.
Dickersin said that while research reviews often serve as guidance tools for doctors in clinical practice, they should also help researchers identify unanswered questions. "It is still unclear which women gain the most benefit from the inclusion of taxanes," Nowak said.
Also unknown is whether taxanes are more beneficial to women whose tumors grow in response to the hormone estrogen or to those whose tumors are not hormone-sensitive, and whether these drugs are more or less effective in women with certain genetic predispositions to the disease.
Nowak and one of the other four review authors report that drug companies that manufacture taxanes have previously paid them for some travel expenses and lectures. Dickersin -- who is director of the U.S. Cochrane Center, one of 12 such centers around the world -- said that Cochrane rules on allowable potential conflicts of interest are much stricter than other guidelines, including those of many medical journals and organizations.
Ferguson T, et al. Taxanes for adjuvant treatment of early breast cancer (Review). Cochrane Database of Systematic Reviews 2007, Issue 4.
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