Cochrane Review Gives Green Light to Tailoring Taxanes to Individuals

October 18, 2007 — The newest Cochrane review shows there are many effective taxane regimens for breast cancer patients and clinicians are fortunate to have a variety of options on hand when administering these drugs. "This allows physicians to tailor the regimen to the individual patient in terms of side effects, duration, and convenience," senior author Anna Nowak, MD, from the Sir Charles Gardiner Hospital and University of Western Australia told Medscape Oncology. The Cochrane Collaboration is an international organization that evaluates medical research.
"Clinicians will also find it reassuring that secondary leukemias are not increased among women receiving taxanes — at least with the current length of follow-up of these trials," she said. The researchers report that substituting a taxane for an anthracycline drug can decrease the likelihood of cardiac toxicity. Information, Dr. Nowak says, that should also help clinicians choose a safer regimen in women who may be at higher risk for this complication.
The review compared chemotherapy regimes using taxanes with those that did not and comprised 12 studies of 21,191 women. The taxanes include paclitaxel (Taxol; Bristol-Myers Squibb) and docetaxel (Taxotere; sanofi-aventis).
The review showed the drugs increased survival rates when used as part of chemotherapy following surgery for early-stage breast cancer. Taxanes increased overall survival by 2.6% and survival with no recurrence by 4.1% compared with regimens without taxanes.
There appeared to be a slight advantage to docetaxel, but the reviewers caution this type of analysis cannot accurately compare one drug to another. "This hypothesis would be better tested in a clinical trial directly comparing the 2 drugs," they write. Such trials are ongoing and are expected to be included in future reviews.
Taxanes Added to Chemotherapy After Surgery Improved Survival
"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," Dr. Nowak said in a news release promoting the study.
Some researchers have argued that taxanes provide no advantage over other kinds of chemotherapy, and the results of previous trials have shown that more courses and longer duration chemotherapy in general was better. "These have been past criticisms of some of the earlier taxane trials," Dr. Nowak said. "I think that hypothesis has been disproved by this study."
Commenting in the same news release, Kay Dickersin, PhD, and director of the Center for Clinical Trials at the Johns Hopkins School of Medicine said, "It looks like taxanes are beneficial." Dr. Dickersin, who was not involved with the review, added that the studies analyzed appeared to be of good quality, which strengthens the result.
"This was not an individual patient meta-analysis," Dr. Nowak pointed out to Medscape Oncology, "and we were unable to look at the benefits of taxanes in specific patient subgroups such as women with estrogen- and progesterone-receptor positive or HER2/neu positive breast cancer."
She noted that further research is needed to define which patients will benefit the most from the inclusion of a taxane in adjuvant chemotherapy. "Ongoing clinical trials will also help define the best taxane drug to use, how long to use it for, and which drugs to combine it with," Dr. Nowak said.
The review did confirm that certain adverse effects were higher among those treated with taxanes. These included neurotoxicity — in this case, numbness, tingling, or weakness in hands and feet — and febrile neutropenia.
There were also lower rates of nausea among those treated with taxanes, some regimens were found to be less harmful to the heart, and the researchers observed no additional treatment-related deaths in the taxane group.
"A next generation of studies is required to further define the precise role of taxanes as adjuvant chemotherapy for early breast cancer," write the reviewers. They await information from ongoing and future randomized trials comparing docetaxel with paclitaxel for additional direction on dose density, scheduling, and duration.
The reviewers would also like more information on how best to combine taxane and anthracycline-based treatment and on how to combine taxanes with trastuzumab in women with HER2-positive disease.
Senior author Dr. Nowak has disclosed receiving educational travel grants from Bristol-Myers-Squibb and sanofi-aventis. Coauthor Dr. Wilcken has disclosed receiving honoraria from Aventis.
Cochrane Database Syst Rev. Published online October 17, 2007.