Advertisement

Clinical and Translational Oncology

, Volume 21, Issue 2, pp 239–245 | Cite as

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

  • O. Abdel-RahmanEmail author
Brief Research Article
  • 50 Downloads

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

Chemotherapy Dose intensity Relative dosing intensity Breast cancer 

Notes

Acknowledgements

This publication is based on research using information obtained from http://www.projectdatasphere.org, which is maintained by Project Data Sphere, LLC. Neither Project Data Sphere, LLC nor the owner(s) of any information from the website have contributed to, approved or are in any way responsible for the contents of this publication.

Funding

This study was not funded.

Compliance with ethical standards

The current study is fully compliant with all applicable ethical and legal standards. It complies fully with the Declaration of Helsinki.

Conflict of interest

None.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author. The original study was approved by appropriate ethics committees of the participating institutes (as detailed in the published clinical trial report and clinicaltrials.gov report of this trial).

Informed consent

As this study is based on a publicly available dataset without identifying patient information, informed consent was not needed. Informed consent was, however, obtained from each of the participants of the original study (as detailed in the published clinical trial report and clinicaltrials.gov report of this trial).

References

  1. 1.
    Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2015;26(suppl_5):v8–30.  https://doi.org/10.1093/annonc/mdv298.CrossRefGoogle Scholar
  2. 2.
    Shannon C, Ashley S, Smith IE. Does timing of adjuvant chemotherapy for early breast cancer influence survival? J Clin Oncol. 2003;21(20):3792–7.  https://doi.org/10.1200/jco.2003.01.073.CrossRefGoogle Scholar
  3. 3.
    Lohrisch C, Paltiel C, Gelmon K, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006;24(30):4888–94.  https://doi.org/10.1200/jco.2005.01.6089.CrossRefGoogle Scholar
  4. 4.
    Cold S, During M, Ewertz M, et al. Does timing of adjuvant chemotherapy influence the prognosis after early breast cancer? Results of the Danish Breast Cancer Cooperative Group (DBCG). Br J Cancer. 2005;93(6):627–32.  https://doi.org/10.1038/sj.bjc.6602734.CrossRefGoogle Scholar
  5. 5.
    Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995;332(14):901–6.  https://doi.org/10.1056/nejm199504063321401.CrossRefGoogle Scholar
  6. 6.
    Abdel-Rahman O. Assessment of the prognostic and discriminating value of the novel bioscore system for breast cancer; a SEER database analysis. Breast Cancer Res Treat. 2017.  https://doi.org/10.1007/s10549-017-4244-2.Google Scholar
  7. 7.
  8. 8.
    Eiermann W, Pienkowski T, Crown J, et al. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011;29(29):3877–84.  https://doi.org/10.1200/jco.2010.28.5437.CrossRefGoogle Scholar
  9. 9.
    Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979;63(11–12):1727–33.Google Scholar
  10. 10.
    Zhu X, Bouganim N, Vandermeer L, et al. Use and delivery of granulocyte colony–stimulating factor in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy—single-centre experience. Curr Oncol. 2012;19(4):e239–43.  https://doi.org/10.3747/co.19.948.CrossRefGoogle Scholar
  11. 11.
    Becker DJ, Talwar S, Levy BP, et al. Impact of oncology drug shortages on patient therapy: unplanned treatment changes. J Oncol Pract. 2013;9(4):e122–8.  https://doi.org/10.1200/JOP.2012.000799.CrossRefGoogle Scholar
  12. 12.
    Zhang L, Yu Q, Wu X-C, et al. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative. Breast Cancer Res. 2018.  https://doi.org/10.1007/s10549-017-4646-1.Google Scholar
  13. 13.
    Chirivella I, Bermejo B, Insa A, et al. Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat. 2009;114(3):479–84.  https://doi.org/10.1007/s10549-008-0018-1.CrossRefGoogle Scholar
  14. 14.
    Bines J, Earl H, Buzaid AC, et al. Anthracyclines and taxanes in the neo/adjuvant treatment of breast cancer: does the sequence matter? Ann Oncol. 2014;25(6):1079–85.  https://doi.org/10.1093/annonc/mdu007.CrossRefGoogle Scholar
  15. 15.
    Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008;358(16):1663–71.  https://doi.org/10.1056/NEJMoa0707056.CrossRefGoogle Scholar
  16. 16.
    Veitch ZWN, Khan OF, Tilley D, et al. Adjustments in relative dose intensity (RDI) for FECD chemotherapy in breast cancer: a population analysis. J Clin Oncol. 2017;35(15_suppl):547.  https://doi.org/10.1200/jco.2017.35.15_suppl.547.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Clinical Oncology Department, Faculty of MedicineAin Shams UniversityCairoEgypt
  2. 2.Department of OncologyUniversity of Calgary and Tom Baker Cancer CenterCalgaryCanada

Personalised recommendations