Outcomes of early-stage breast cancer patients treated with sequential anthracyclines-taxanes in relationship to relative dosing intensity: a secondary analysis of a randomized controlled trial

Clin Transl Oncol. 2019 Feb;21(2):239-245. doi: 10.1007/s12094-018-1915-3. Epub 2018 Jun 28.

Abstract

Purpose: To assess the impact of relative dosing intensity (RDI) on the outcomes of breast cancer patients referred for adjuvant anthracycline-taxane chemotherapy.

Methods: This is a secondary analysis of the outcomes of patients in the comparator arm of the BCIRG005 study who received adjuvant adriamycin/cyclophosphamide (AC)-docetaxel regimen. Overall survival was assessed according to RDI through Kaplan-Meier analysis. Univariate and multivariate analyses of parameters affecting overall survival were then conducted through Cox regression analysis.

Results: Kaplan-Meier analysis of overall survival according to RDI for the AC-docetaxel regimen (< 90 vs. ≥ 90%) was conducted and it showed that RDI < 90% is associated with worse overall survival (P = 0.006). In univariate Cox regression analysis, the following parameters significantly affected overall survival (P < 0.05): age, T stage, lymph node ratio, hormone receptor status, and grade of the disease and RDI for AC-docetaxel regimen. When these factors were included in multivariate analysis, the following factors were associated with worse overall survival: age less than 40 years (P < 0.0001), greater T stage (P < 0.0001), greater lymph node ratio (P < 0.0001), negative hormone receptor status (P = 0.001), high grade (P < 0.0001) and RDI ≤ 90% (P = 0.015). Formal interaction testing between RDI and hormone receptor status has a non-significant P value (P = 0.794).

Conclusion: Lower RDI for the whole anthracycline-taxane protocol is associated with worse patient survival. Every effort should be exercised to avoid unnecessary dose reductions and/or interruptions among early breast cancer patients receiving adjuvant anthracycline-taxane chemotherapy.

Keywords: Breast cancer; Chemotherapy; Dose intensity; Relative dosing intensity.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Clinical Trials, Phase III as Topic
  • Cyclophosphamide / administration & dosage*
  • Disease-Free Survival
  • Docetaxel / administration & dosage*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Retrospective Studies

Substances

  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide