The chemotherapy medicine Taxotere (chemical name: docetaxel) is approved to be used in combination with other chemotherapy medicines to treat early-stage breast cancer. Still, doctors continued to study exactly how beneficial Taxotere was in treating early-stage breast cancer.
The large study reviewed here found that women diagnosed with early-stage breast cancer who got Taxotere after one of two standard chemotherapy regimens did about the same as women who didn't get Taxotere. The women who got Taxotere were more likely to have serious side effects because of the Taxotere.
Chemotherapy often is used after breast cancer surgery to reduce the risk of breast cancer coming back. This type of chemotherapy -- called adjuvant chemotherapy -- aims to weaken and destroy any cancer cells that may be left behind after surgery.
More than 4,000 women diagnosed with early-stage breast cancer in Great Britain participated in the study. All the women received one of two standard adjuvant chemotherapy regimens after surgery:
After receiving one of these two standard regimens, half of the women also got Taxotere.
The researchers found:
Even though this study didn't show any overall benefits to making Taxotere part of adjuvant chemotherapy to treat early-stage breast cancer, the researchers pointed out that the way individual cancers respond to Taxotere can vary widely. So other research might show that early-stage breast cancers with certain characteristics will respond to Taxotere.
Taxotere also is approved to treat advanced and metastatic breast cancer after other chemotherapy medicines have stopped working. This study didn't look at using Taxotere to treat advanced/metastatic breast cancer.
If you've been diagnosed with early-stage breast cancer, your treatment plan will take into account your unique situation and any research results that pertain to your situation. If your doctor recommends including Taxotere in your adjuvant chemotherapy treatment plan, ask how the results of the study reviewed here might apply to your situation. Together, you and your doctor can decide on the treatment plan that is best for YOU.
WHEELING, W.Va., May 15 (MedPage Today) -- Adding docetaxel (Taxotere) to standard anthracycline-based adjuvant chemotherapy failed to improve five-year survival or recurrence of breast cancer in a large randomized trial, British researchers said.
Disease-free survival after a median of 62 months was 75.6% (95% CI 73.7% to 77.5%) in patients receiving docetaxel plus standard chemotherapy, compared with 74.3% (95% CI 72.3% to 76.2%) in patients who did not get docetaxel.
The trial involved more than 4,100 patients, Paul Ellis, M.D., of Guy's Hospital in London, and colleagues reported in the May 16 issue of The Lancet.
The study is the largest to date to test taxanes as part of primary adjuvant therapy in early-stage breast cancer, the researchers said.
"The findings reported here suggest a smaller effect from the incorporation of docetaxel into adjuvant breast cancer treatment than might have been expected based on worldwide evidence to date," they wrote.
Earlier trials with paclitaxel (Taxol) or docetaxel had found a modest survival benefit, Dr. Ellis and colleagues noted.
The variation in results suggests there may be patient subgroups that would profit from taxanes in adjuvant therapy, they said.
"We support the view that 'one-size-fits-all' adjuvant chemotherapy trials in early breast cancer are too simple," the researchers said.
"We propose that future trials are designed around specific biological patient subgroups, with the aim of accelerating advances in tailored therapy."
The current study, called TACT (Taxotere as Adjuvant Chemotherapy Trial), involved 4,162 women with node-positive or high-risk node-negative operable early-stage breast cancer.
As is customary, the patients received adjuvant chemotherapy following complete surgical excision of tumors.
About half were assigned to receive four cycles of docetaxel (open-label) following four cycles of standard therapy including 5-fluorouracil, epirubicin, and cyclophosphamide (FEC).
Control patients received either that standard regimen or another based on cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), depending on which clinic they attended.
The conventional regimens were delivered every four weeks. Docetaxel was given at 100 mg/m2 at three-week intervals.
Five-year disease-free survival was the primary endpoint. Overall survival was also reported, as were adverse events.
The hazard ratio for recurrence or death with add-on docetaxel within five years was 0.95 (95% CI 0.85 to 1.08).
Kaplan-Meier curves for disease-free and overall survival in the docetaxel and control groups were almost completely superimposed, highlighting the taxane's apparent ineffectiveness.
Moreover, the docetaxel patients were more likely to suffer grade 3 or 4 toxicities.
In centers using FEC as the control regimen, 69% of patients receiving docetaxel experienced grade 3 or 4 events compared with 60% of those treated with FEC alone (P<0.0001).
Neutropenia (febrile or not), leukopenia, diarrhea, infection, lethargy, muscle and joint pain, neuropathy, edema, stomatitis, and dermal effects were each significantly more common with docetaxel.
Similar findings were reported at centers using the CMF control.
Among 829 patients whose quality of life was evaluated, adjuvant therapy was associated with significant impairment.
Deterioration in quality of life was significantly worse with docetaxel overall and for most subscales, except that nausea and vomiting was more of a problem for control patients.
Group differences in quality of life decreased as time went on and returned nearly to baseline levels after two years, the researchers said.
Despite the lack of benefit seen for docetaxel in TACT, Dr. Ellis and colleagues said, "the long-term benefits of taxanes need further evaluation."
They noted that the risk of recurrence remains substantial for at least 15 years.
"Further follow-up is needed before a possible longer term benefit can be identified or excluded in this patient population," the researchers wrote.
In an accompanying editorial, Miguel Martin, M.D., of Hospital Clinico San Carlos in Madrid, speculated that "administration of FEC in the experimental group of TACT could have jeopardized the efficacy of docetaxel by inducing multidrug resistance."
However, he added, "the real reason for the lack of significant differences between groups remains unresolved. The only clear lesson from TACT is that the FEC-D is not superior to a conventional, less toxic adjuvant treatment, and should not be recommended as an adjuvant treatment for early breast cancer."
The study was funded by Cancer Research UK, sanofi-aventis, Pfizer, and Roche.
Several study authors reported relationships (other than research support) with Pfizer, Roche, and sanofi-aventis.
Dr. Martin disclosed that he has received consultancy and speakers' fees from Pfizer, sanofi-aventis, Bristol-Myers Squibb, and Roche.
Primary source: The Lancet Source reference: Ellis P, et al "Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial" Lancet 2009; 373: 1681-92.
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