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Combination of capecitabine and docetaxel did not reduce recurrence in operable breast cancer
Kelly CM. J Clin Oncol. 2012;doi:10.1200/JCO.2011.36.2079.
The substitution of capecitabine plus docetaxel for weekly paclitaxel followed by fluorouracil, epirubicin and cyclophosphamide did not have a positive effect on recurrence-free survival in patients with operable breast cancer, according to the results of a phase 3 study.
Researchers who conducted this single institution study posited that the use of capecitabine would “enhance the antitumor activity of docetaxel,” resulting in improved efficacy of standard treatments.
To test this hypothesis, the researchers enrolled 601 patients with histologically-confirmed invasive breast cancer. Between 2002 and 2008, the patients were randomly assigned to one of two treatment regimens:
l weekly paclitaxel (WP) for 12 weeks followed by fluorouracil, epirubicin and cyclophosphamide (FEC) every 3 week for four cycles.
l docetaxel on day 1 and capecitabine (XT) on days 1 to 14 every 3 weeks for four cycles, followed by FEC for four cycles.
The primary outcome of the study was recurrence-free survival.
After a median follow-up of 50 months, there was no difference in recurrence-free survival for patients treated with XT vs. WP (87.5% vs. 90.7%). In addition, there was no difference between treatment arms for pathologic complete response or breast-conserving surgery.
Patients who were assigned to XT had a significantly higher rate of stomatitis, hand-foot syndrome and neutropenic infection.
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Randomized data showing superiority (tumor response rates, time to disease progression and OS) for the addition of capecitabine to docetaxel in the treatment of metastatic breast cancer led to great interest in utilizing capecitabine plus taxane combinations to hopefully improve outcomes in early breast cancer. However, the initial enthusiasm for incorporating capecitabine into standard anthracycline- and taxane-based adjuvant chemotherapy has been tempered by the negative results from the well-designed and well-powered FinXX (TX/CEX vs. T/CEF) and US Oncology 01062 (AC-TX vs. AC-TX) clinical trials. This report showing equivalent efficacy but differing toxicities between capecitabine plus paclitaxel/docetaxel followed by anthracycline does not change how I currently treat early breast cancers, since the widespread addition of capecitabine to anthracycline- and taxane-based adjuvant chemotherapy confers no therapeutic advantage.
The expansive application of additional so-called non-cross reactive cytotoxic agents to the broad category of “high-risk early breast cancers” has been disappointing. For instance, the addition of gemcitabine to standard anthracycline- and taxane-based adjuvant chemotherapy also did not improve outcomes in the tAnGo clinical trial (paclitaxel, anthracycline, gemcitabine and cyclophosphamide). Does this mean that capecitabine and gemcitabine are not active in early breast cancer? I suspect that capecitabine, gemcitabine, and many other current and novel cytotoxic agents will have a role in improving adjuvant outcomes in the future for certain yet-to-be determined subtypes of tumors. However, rather than simply treating everyone with these agents, we will need to develop genomic and biomarker tools to identify exactly which individual tumors should be treated with precisely what specific agents.
Stephen Y. Chui, MD
HemOnc Today Editorial Board member
Disclosure: Dr. Chui reports no relevant financial disclosures.