Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial

Background Chemotherapy drug distribution varies greatly among individual p atients. Therefore, we developed an individualised fluorouracil. epirubicin , cyclophosphamide (FEC) regimen to improve outcomes in patients with high- risk early breast cancer. We then did a randomised trial to compare this in dividually tailored FEC regimen with conventional adjuvant chemotherapy fol lowed by consolidation with high-dose chemotherapy with stem-cell support. Methods 525 women younger than 60 years of age with highrisk primary breast cancer were randomised after surgery to receive nine cycles of tailored FE C to haematological equitoxicity with granulocyte colony-stimulating factor (G-CSF) support (n=251), or three cycles of FEC at standard doses followed by high-dose chemotherapy with cyctophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Bot h groups received locoregional radiation therapy and tamoxifen for 5 years. The primary outcome measure was relapse-free survival, and analysis was by intention to treat. Findings At a median follow-up of 34.3 months, there were 81 breast-cancer relapses in the tailored FEC group versus 113 in the CTCb group (double tri angular method p=0.04). 60 deaths occurred in the tailored FEC group and 82 in the CTCb group (log-rank p=0.12). Patients in the CTCb group experience d more grade 3 or 4 acute toxicity compared with the tailored FEC group (p< 0.0001). Two treatment-related deaths (0.7%) occurred in the CTCb group. Si x patients in the tailored FEC group developed acute myeloid leukaemia and three developed myelodysplastic syndrome. Interpretation Tailored FEC with G-CSF support resulted in a significantly improved relapse-free survival and fewer grade 3 and 4 toxicities compared with marrow-supported high-dose chemotherapy with CTCb as adjuvant therapy of women with high-risk primary breast cancer.