Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: A randomized clinical trial

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


IMPORTANCE Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy.Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. OBJECTIVE To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. DESIGN, SETTING, AND PARTICIPANTS A randomized, open-label, phase 3 trial ofwomen aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. INTERVENTIONS Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. MAIN OUTCOMES AND MEASURES The primary end pointwas breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. RESULTS Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97%with node-positive disease), 2000 received study treatment (1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95%CI, 0.61-1.01; log-rank P =.06; 5-year BCRFS, 88.7%vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95%CI, 0.63-0.99; P =.04; 5-year EFS, 86.7%vs 82.1%). The groups did not differ in OS (HR, 0.77; 95%CI, 0.57-1.05; P =.09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95%CI, 0.64-1.08; P =.17; 5-year DDFS, 89.4%vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group. CONCLUSIONS AND RELEVANCE Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.


  • Theodoros Foukakis
  • Gunter Von Minckwitz
  • Nils Olof Bengtsson
  • Yvonne Brandberg
  • Birgitta Wallberg
  • Tommy Fornander
  • Brigitte Mlineritsch
  • Sabine Schmatloch
  • Christian F. Singer
  • Günther Steger
  • Daniel Egle
  • Eva Karlsson
  • Lena Carlsson
  • Sibylle Loibl
  • Michael Untch
  • Mats Hellström
  • Hemming Johansson
  • Harald Anderson
  • Michael Gnant
  • Richard Greil
  • Volker Möbus
  • Jonas Bergh
Enheter & grupper
Externa organisationer
  • Karolinska University Hospital
  • German Breast Group
  • Norrland University Hospital
  • Elisabethhospital (Kassel)
  • Medical University of Vienna
  • Medical University of Innsbruck
  • Karlstad Hospital
  • Sundsvall Hospital
  • HELIOS Klinikum Berlin-Buch
  • Skåne University Hospital
  • Klinikum Frankfurt Höchst
  • Paracelsus Private Medical University of Salzburg

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Sidor (från-till)1888-1896
TidskriftJAMA: The Journal of the American Medical Association
Utgåva nummer18
StatusPublished - 2016 nov 8
Peer review utfördJa