Five‐year results of a phaseIItrial of preoperative 5‐fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab inHER2‐positive patients) for patients with stageIIorIIIbreast cancer
Authors: Holmes Frankie Ann , Hellerstedt Beth A. , Pippen John E. , Vukelja Svetislava J. , Collea Rufus P. , Kocs Darren M. , Blum Joanne L. , McIntyre Kristi J. , Barve Minal A. , Brooks Barry D. , Osborne Cynthia R. , Wang Yunfei , Asmar Lina , O'Shaughnessy Joyce 
Published: March 2018

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 withHER2‐positive disease) and to evaluate 5‐year disease‐free survival (DFS) associated with this preoperative regimen. Chemotherapy included four cycles ofFEC100 (5‐fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2IVon 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/m2orally twice daily for 14 days followed by 7 days off) (wTX). ForHER2‐positive patients, treatment was modified by decreasing epirubicin to 75 mg/m2and adding trastuzumab (H) in standard doses (FEC75‐H →wTX‐H). The study objective was to achieve apCRrate in the breast and axillary lymph nodes of 37% in patients withHER2‐negative breast cancer and of 67% in patients withHER2‐positive breast cancer treated with preoperative trastuzumab. A total of 186 patients were enrolled on study. In an intent‐to‐treat analysis, thepCRrate was 31% (37/118, 95%CI: 24–40%) in theHER2‐negative patients, 24% (15/62, 95%CI: 14–37%) inER‐positive/HER2‐negative patients, 39% (22/56, 95%CI: 27–53%) in theER‐negative/HER2‐negative patients, and 46% (29/63, 95%CI: 34–48%) in theHER2‐positive patients. ThepCRrate 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 theHER2‐negative population (78% inER‐positive/HER2‐negative and 62% in theER‐negative/HER2‐negative patients) and 80% in theHER2‐positive patients (87% in the trastuzumab‐treatedHER2‐positive patients). At 5 years, overall survival was 80% in theHER2‐negative population (88% inER‐positive/HER2‐negative and 71% in theER‐negative/HER2‐negative patients) and 86% in theHER2‐positive patients (94.5% in the trastuzumab‐treatedHER2‐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 followingFEC, with or without trastuzumab, did not increasepCRrates nor 5‐yearDFSover 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.