Open AccessFive‐year results of a phase II trial of preoperative 5‐fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine ( wTX ) (with trastuzumab in HER 2‐positive patients) for patients with stage II or III breast cancer
Author(s) -
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
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1472
Subject(s) - epirubicin , docetaxel , capecitabine , medicine , trastuzumab , fluorouracil , cyclophosphamide , regimen , breast cancer , chemotherapy , oncology , gastroenterology , urology , surgery , cancer , colorectal cancer
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 HER 2‐positive disease) and to evaluate 5‐year disease‐free survival ( DFS ) associated with this preoperative regimen. Chemotherapy included four cycles of FEC 100 (5‐fluorouracil 500 mg/m 2 , epirubicin 100 mg/m 2 , cyclophosphamide 500 mg/m 2 IV on Day 1 every 21 days) followed by 4 21‐day cycles of docetaxel (35 mg/m 2 days 1 and 8) concurrently with capecitabine (825 mg/m 2 orally twice daily for 14 days followed by 7 days off) ( wTX ). For HER 2‐positive patients, treatment was modified by decreasing epirubicin to 75 mg/m 2 and adding trastuzumab (H) in standard doses ( FEC 75‐H → wTX ‐H). The study objective was to achieve a pCR rate in the breast and axillary lymph nodes of 37% in patients with HER 2‐negative breast cancer and of 67% in patients with HER 2‐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 HER 2‐negative patients, 24% (15/62, 95% CI : 14–37%) in ER ‐positive/ HER 2‐negative patients, 39% (22/56, 95% CI : 27–53%) in the ER ‐negative/ HER 2‐negative patients, and 46% (29/63, 95% CI : 34–48%) in the HER 2‐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 HER 2‐negative population (78% in ER ‐positive/ HER 2‐negative and 62% in the ER ‐negative/ HER 2‐negative patients) and 80% in the HER 2‐positive patients (87% in the trastuzumab‐treated HER 2‐positive patients). At 5 years, overall survival was 80% in the HER 2‐negative population (88% in ER ‐positive/ HER 2‐negative and 71% in the ER ‐negative/ HER 2‐negative patients) and 86% in the HER 2‐positive patients (94.5% in the trastuzumab‐treated HER 2‐positive patients). FEC 100 ( FEC 75 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.