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

Abstract

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m²) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m²) and 5-fluorouracil (500 mg/m²) on days 1 and 8 and cyclophosphamide (75 mg/m²) on days 1–14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.

Adipocyte/breast cancer cell crosstalk in obesity interferes with the anti-proliferative efficacy of tamoxifen

“…The higher risk of recurrence and mortality in obese patients could be related to a lesser efficacy of anti-cancer treatments probably due to plasma adipokine variations linked to overweight. Indeed, obese breast cancer women are less sensitive to chemotherapy [ 12 ] and present higher mortality rates [ 13 – 15 ]. MDA-MB-231 mammary cancer cells treated with adipose stem cell supernatants present resistance to doxorubicin [ 16 ].…”

Adjuvant Chemotherapy for Early Female Breast Cancer: A Systematic Review of the Evidence for the 2014 Cancer Care Ontario Systemic Therapy Guideline

“…Some studies 31,38 examined drugs not commonly used in Canada for the treatment of breast cancer. Several studies 53,54,[56][57][58] used the fec regimen with or without taxanes and with doses of epirubicin less than 100 mg/m 2 ; they are thus not relevant to practice in Ontario. A few publications presented trial subgroup analyses or molecular studies.…”

“…In the present evidence review, trials of taxanes represented the largest number of rcts (fifty-five trials in ninety-three publications) and are summarized in Supplemental Table 3 21,27-30,35,36, [49][50][51][52][53][54] . Because taxane studies are relatively recent, our database search found most of the published trials cited in other reviews or meta-analyses.…”

“…Taxanes and Other Chemotherapy Drugs Several studies 53,54,[56][57][58] used the fec regimen with or without taxanes and with epirubicin doses less than 100 mg/m 2 and thus are not relevant to practice in Ontario. Based on the finher study 57 , vinorelbine is inferior to docetaxel when followed by fec.…”

Estimation of Risk of Recurrence and Toxicity Among Oncologists and Patients With Resected Breast Cancer: A Quantitative Study

“…(Dooley et al, 2017) that add to their fear of recurrence (Miroševič et al, 2019). In recent years, other factors, such as tumor grade, estrogen receptor, and progesterone receptor status, HER2 overexpression, and, in some cases, genomic profiles, have been added to the prognostic value of TNM staging based on tumor size (T), number of regional lymph nodes affected (N), and the presence or absence of distant metastases (M), yielding more robust and precise prognostic information (Schönherr et al, 2012;Piñeros et al, 2019). Physicians estimate risk of adjuvant treatment-associated toxicity on the rates of side effects reported in clinical trials.…”