We aimed to increase
pathologic complete response (pCR) in patients with invasive
breast cancer by adding preoperative
capecitabine to
docetaxel following
5-fluorouracil,
epirubicin,
cyclophosphamide (FEC) (with
trastuzumab for patients with HER2-positive disease) and to evaluate 5-year disease-free survival (DFS) associated with this preoperative regimen.
Chemotherapy included four cycles of FEC100 (
5-fluorouracil 500 mg/m2 ,
epirubicin 100 mg/m2 ,
cyclophosphamide 500 mg/m2 IV on Day 1 every 21 days) followed by 4 21-day cycles of
docetaxel (35 mg/m2 days 1 and 8) concurrently with
capecitabine (825 mg/m2 orally twice daily for 14 days followed by 7 days off) (wTX). For HER2-positive patients, treatment was modified by decreasing
epirubicin to 75 mg/m2 and adding
trastuzumab (H) in standard doses (FEC75-H →wTX-H). The study objective was to achieve a pCR rate in the breast and axillary lymph nodes of 37% in patients with HER2-negative
breast cancer and of 67% in patients with HER2-positive
breast cancer treated with preoperative
trastuzumab. A total of 186 patients were enrolled on study. In an intent-to-treat analysis, the pCR rate was 31% (37/118, 95% CI: 24-40%) in the HER2-negative patients, 24% (15/62, 95% CI: 14-37%) in ER-positive/HER2-negative patients, 39% (22/56, 95% CI: 27-53%) in the ER-negative/HER2-negative patients, and 46% (29/63, 95% CI: 34-48%) in the HER2-positive patients. The pCR rate in the 40
trastuzumab-treated patients was 53% (21/40, 95% CI: 38-67%). Grade 3 and 4 adverse events included
neutropenia,
leukopenia,
diarrhea, and hand-foot skin reactions. One
trastuzumab-treated patient developed grade 3
cardiotoxicity, and 4 others experienced grade 1-2 decrements in left ventricular function; all five patients' cardiac function returned to their baseline upon completion of
trastuzumab. At 5 years, disease-free survival was 70% in the HER2-negative population (78% in ER-positive/HER2-negative and 62% in the ER-negative/HER2-negative patients) and 80% in the HER2-positive patients (87% in the
trastuzumab-treated HER2-positive patients). At 5 years, overall survival was 80% in the HER2-negative population (88% in ER-positive/HER2-negative and 71% in the ER-negative/HER2-negative patients) and 86% in the HER2-positive patients (94.5% in the
trastuzumab-treated HER2-positive patients). FEC100 (FEC75 with
trastuzumab) followed by weekly
docetaxel plus
capecitabine, with or without
trastuzumab is a safe, effective preoperative cytotoxic regimen. However, the addition of
capecitabine to
docetaxel following FEC, with or without
trastuzumab, did not increase pCR rates nor 5-year DFS over the rates that have been reported with standard preoperative
doxorubicin/
cyclophosphamide (AC) followed by
paclitaxel, with or without
trastuzumab. Therefore, the use of
capecitabine as part of preoperative
chemotherapy is not recommended.