FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG)

Abstract

International audienceA randomized multicenter phase III study was conducted to compare the sequential docetaxel followed by epirubicin/cyclophosphamide combination with that of FEC regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer. Seven hundred and fifty-six women with axillary lymph node-positive breast cancer were randomized to receive either 4 cycles of docetaxel (100 mg/m) followed by 4 cycles of epirubicin (75 mg/m) plus cyclophosphamide (700 mg/m) (experimental arm) or 6 cycles of FEC (epirubicin 75 mg/m, cyclophosphamide 700 mg/m, and 5-fluorouracil 700 mg/m; control arm). All regimes were administered every 3 weeks. The primary end point was five-year disease-free survival (DFS). After a median follow-up period of 5 years, 233 (30.8%) relapses had occurred (108 and 125 in the experimental and control arms, respectively; = 0.181). The five-year DFS was 72.6% (95% CI 63.8–81.3%) and 67.2% (95% CI 58.0–76.4%) for women randomized in the experimental and control arms, respectively ( = 0.041; log rank test). There was no difference in the overall survival between the two arms (83.8 and 81.4% in the experimental and control arms, respectively; = 0.533). The experimental arm was associated with increased neutropenia requiring administration of granulocyte colony-stimulating factor in 90.5% of the patients as compared with 74.1% in the control arm ( = 0.0001). The sequential docetaxel followed by epirubicin/cyclophosphamide adjuvant chemotherapy regimen resulted in improved five-year DFS in women with axillary node-positive early breast cancer at the expense of increased but manageable myelotoxicity

Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

“…Hematological toxicity and its complications are the greatest challenge in adjuvant chemotherapy for breast cancer. Our data analysis has shown that hematological toxicity, especially neutropenia, is the main side effect of anthracycline and taxane-based chemotherapy, as also observed in the NSABP-B-28 and the PACS-01 trials [10,12,21]. We found myelotoxicity to be the most common toxicity of grade 3/4 for both groups.…”

“…In summary, taxanes have been shown in various trials to be a feasible treatment option [15,21,24]. Pooled data on the side effects from 4 trials (including the ADEBAR trial) demonstrate that taxane-containing chemotherapy is acceptable even for elderly patients [25].…”

“…Primary application of G-CSF or pegfilgastrim in other docetaxel regimens could have influenced the comparability of the toxicity data [22]. According to the PACS 01 trial, anemia and thrombocytopenia were not the main complications resulting from taxane-based therapy [12,21], while these complications occurred more often during FEC therapy. Overall, hematological toxicity was seen to be the most frequent side effect in FEC120 therapy.…”

Hypersensitivity Reactions to Docetaxel: Retrospective Evaluation and Development of a Desensitization Protocol

“…Taxanes – paclitaxel and semisynthetic docetaxel (DT) – are approved as first-line treatment for non-small cell lung cancer (NSCLC) [6,7], breast [8,9] and ovarian [10] carcinomas and are also used in the treatment of numerous other malignancies [11,12,13,14,15]. Paclitaxel is a natural alkaloid isolated from Taxus brevifolia, whereas DT is a semi-synthetic compound produced from 10-deacetylbaccatin III found in Taxus baccata [16].…”

Does the sequence of taxane administration affect the outcome of patients with breast cancer in the adjuvant and neoadjuvant settings?

“…Recently, there has been a concern about the sequencing of these two drugs. In a recent randomized phase III study by the Hellenic Oncology Research Group, three weekly docetaxel followed by epirubicin/cyclophosphamide (E/C) combination was compared with epirubicin/cyclophosphamide/5-fluorouracil (FEC) regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer (1). Five-year disease-free survival was found to be better in the sequential docetaxel followed by E/C group (72.6 vs. 67.2%, P = 0.041).…”