A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1). (May 2018)

• Record Type: Journal Article
• Authors: Lindman, H.; Andersson, M.; Ahlgren, J.; Balslev, E.; Sverrisdottir, A.; Holmberg, S.B.; Bengtsson, N.O.; Jacobsen, E.H.; Jensen, A.B.; Hansen, J.; Tuxen, M.K.; Malmberg, L.; Villman, K.; Anderson, H.; Ejlertsen, B.; Bergh, J.; Blomqvist, C.
• Is Part Of: European journal of cancer. Volume 94(2018)
• Page Start: 79
• Page End: 86
• Publication Date: 2018-05
• Subjects: Adjuvant -- Breast cancer -- Chemotherapy -- Dosage -- Dose tailoring -- Leukopenia; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.02.016
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Study aim: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Methods: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m 2, epirubicin 60 mg/m 2, cyclophosphamide 600 mg/m 2 ). Patients with nadir leukopenia grade 0–2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75–90 mg/m 2, C 900–1200 mg/m 2 ) or fixed treatment with 6 standard FEC. Patients with grade 3–4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). Results: The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC ( N = 524) or standard FEC ( N = 528), whereas 401 patients with leukopenia grade 3–4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67–1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57–1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. Conclusions: The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment. Highlights: Tailoring adjuvant chemotherapy dosage based on toxicity was feasible. No significant benefit of dose escalation, except in grade 3 tumours. Outcome implies that sufficient haematological toxicity is more important than dose. Individually tailored dosage of chemotherapy needs further examinations.