Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer

Breast Cancer Res Treat. 2018 Apr;168(2):349-355. doi: 10.1007/s10549-017-4599-4. Epub 2017 Nov 30.

Abstract

Purpose: Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs.

Methods: The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up.

Results: A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up.

Conclusions: In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.

Keywords: Adjuvant chemotherapy; Breast cancer; Dose-dense; Randomized; Tailored dose.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cardiotoxicity / epidemiology
  • Cardiotoxicity / etiology
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms / chemically induced
  • Hematologic Neoplasms / epidemiology
  • Humans
  • Long-Term Care / methods*
  • Lymphatic Metastasis / pathology
  • Mastectomy
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Prospective Studies
  • Young Adult