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

Abstract

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.

Efficacy and Safety of Neoadjuvant Chemotherapy with Dose De-Escalation Tri-Weekly Nanoparticle Albumin-Bound Paclitaxel and FEC for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

“…The risk of anthracyclineinduced cardiotoxicity is dose-dependent and increases with the cumulative dose. To avoid cardiac toxicity, several studies have utilized FEC75, 3,20 which was also applied in our study. In addition, anthracycline-free regimens have been tested for the treatment of selected low-risk tumors.…”

Heterogeneity characterization of hepatocellular carcinoma based on the sensitivity to 5-fluorouracil and development of a prognostic regression model

“…As a synthetic fluorinated pyrimidine analog, 5-fluorouracil (5-FU) enters cells as an anti-metabolite, imitates molecules vital to cell growth, interferes with basic biosynthetic activity by inhibiting the effect of thymidylate synthase (TS), or mistakenly mixes its metabolites into DNA and RNA, thereby inducing cytotoxicity ( Blondy et al, 2020 ; Mafi et al, 2023 ). Since its approval by FDA in 1962, 5-FU has been widely applied alone or together with other drugs in treating various cancers, such as advanced head and neck squamous cell carcinoma ( Yamauchi et al, 2023 ), colorectal cancer ( Wosiak et al, 2023 ), gastric cancer ( Kang et al, 2014 ), and metastatic breast cancer ( Karapetis et al, 1999 ; Holmes et al, 2018 ). 5-Fu is also a widely used chemotherapeutic drug for patients with HCC.…”