Advanced

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

Lindman, H.; Andersson, M.; Ahlgren, J.; Balslev, E.; Sverrisdottir, A.; Holmberg, S. B.; Bengtsson, N. O.; Jacobsen, E. H.; Jensen, A. B. and Hansen, J., et al. (2018) In European Journal of Cancer 94. p.79-86
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/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). 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/m2, C... (More)

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/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). 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/m2, C 900–1200 mg/m2) 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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adjuvant, Breast cancer, Chemotherapy, Dosage, Dose tailoring, Leukopenia
in
European Journal of Cancer
volume
94
pages
8 pages
publisher
IFAC & Elsevier Ltd.
external identifiers
  • scopus:85043507699
ISSN
0959-8049
DOI
10.1016/j.ejca.2018.02.016
language
English
LU publication?
yes
id
8bd2a596-d3ff-40c8-a87e-372d08c86459
date added to LUP
2018-03-28 11:22:50
date last changed
2019-02-20 11:12:17
@article{8bd2a596-d3ff-40c8-a87e-372d08c86459,
  abstract     = {<p>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<sup>2</sup>, epirubicin 60 mg/m<sup>2</sup>, cyclophosphamide 600 mg/m<sup>2</sup>). 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<sup>2</sup>, C 900–1200 mg/m<sup>2</sup>) 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.</p>},
  author       = {Lindman, H. and Andersson, M. and Ahlgren, J. and Balslev, E. and Sverrisdottir, A. and Holmberg, S. B. and Bengtsson, N. O. and Jacobsen, E. H. and Jensen, A. B. and Hansen, J. and Tuxen, M. K. and Malmberg, L. and Villman, K. and Anderson, H. and Ejlertsen, B. and Bergh, J. and Blomqvist, C. and ,  and ,  and , },
  issn         = {0959-8049},
  keyword      = {Adjuvant,Breast cancer,Chemotherapy,Dosage,Dose tailoring,Leukopenia},
  language     = {eng},
  pages        = {79--86},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1)},
  url          = {http://dx.doi.org/10.1016/j.ejca.2018.02.016},
  volume       = {94},
  year         = {2018},
}