Which is the best chemotherapy adjuvant regimen sequence for early breast cancer?
It is widely known that anthracyclines (epirubicin and doxorubicin) and taxanes is the best adjuvant chemotherapy regimen for early breast cancer. However, should anthracyclines be always administered before taxanes? An article published in the March issue of Lancet Oncology suggested the reverse sequence may be more preferable.
The article, written by Wildiers, provided clear evidences that the taxane-first regimens provided better dose intensity, adverse effects, long-term resistance and survival.
1) Dose Intensity
In a dose sequencing study of 284 patients who first received three cycles of FEC (fluorouracil, epirubicin, and cyclophosphamide) followed by three cycles of docetaxel, the mean relative dose intensity was 91% for FEC and 76% for docetaxel, whereas in another dose sequencing study of 378 patients who received three cycles of docetaxel followed by four cycles of EC (epirubicin plus cyclophosphamide), a median docetaxel dose intensity of 100% was achieved.
2) Adverse effects
Studies have showed that patients who were started with taxane-first adjuvant regimens have fewer skins and grade 4 toxicities. Also, data form the FinHer Trial suggested that the incidence of cardiotoxicity was lower when taxane plus trastuzumab (Herceptin) was given before rather than after anthracyclines.
3) Long-term resistance
An in-vitro study showed that breast cancer cells that were initially resistant to paclitaxel have limited cross-resistance (4 times) to doxorubicin whereas cell lines that were resistant to doxorubicin, exhibited a 4,700-times cross-resistance to paclitaxel.
In a large phase 3 neoadjuvant study, paclitaxel administered before epirubicin-cyclophosphamide (EC) showed a higher complete responses rate than the reverse order.
The above evidences indicated that it is reasonable to administer taxane cycles before anthracycline-containing chemotherapy cycles in the routine clinical setting.
www.thelancet.com/oncology Vol 11 March 2010
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