Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy.

BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.

Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study.

BACKGROUND: Chemotherapy drug distribution varies greatly among individual patients. 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 individually tailored FEC regimen with conventional adjuvant chemotherapy followed by consolidation with high-dose chemotherapy with stem-cell support. METHODS: 525 women younger than 60 years of age with high-risk primary breast cancer were randomised after surgery to receive nine cycles of tailored FEC 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 cyclophosphamide, thiotepa, and carboplatin (CTCb), and peripheral-blood stem-cell or bone-marrow support (n=274). Both 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 triangular 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 experienced 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. Six 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.