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Efficacy of different dosing schedules of capecitabine for metastatic breast cancer: a single-institution experience

  • Anupama Suresh
  • Akannsha Ganju
  • Evan Morgan
  • Marilly Palettas
  • Julie A. Stephens
  • Joseph Liu
  • Michael Berger
  • Craig Vargo
  • Anne Noonan
  • Raquel Reinbolt
  • Mathew Cherian
  • Jeffrey VanDeusen
  • Sagar Sardesai
  • Robert Wesolowski
  • Daniel G. Stover
  • Maryam Lustberg
  • Bhuvaneswari Ramaswamy
  • Nicole WilliamsEmail author
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Summary

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1–14 on 21-day cycle) to biweekly dosing (Arm B: days 1–7 and 15–21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm’s correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–7 and 15–21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

Keywords

Capecitabine Metastatic breast cancer Dosing schedules Survival analysis 

Notes

Acknowledgements

The project described was supported by the Stefanie Spielman Fund for Breast Cancer Research, the Award Number Grant UL1TR002733 from the National Center for Advancing Translational Sciences, and the National Cancer Institute and Cancer Clinical Investigator Team Leadership Award P30CA016058-42S2. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Anupama Suresh, Akannsha Ganju, Evan Morgan, Marilly Palettas, Julie A. Stephens, Joseph Liu, Michael Berger, Craig Vargo, Bhuvaneswari Ramaswamy and Nicole Williams. The first draft of the manuscript was written by Anupama Suresh and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

The project described was supported by the Stefanie Spielman Fund for Breast Cancer Research, the Award Number Grant UL1TR002733 from the National Center for Advancing Translational Sciences, and the National Cancer Institute and Cancer Clinical Investigator Team Leadership Award P30CA016058-42S2. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ohio State University Comprehensive Cancer Center (OSUCCC) Clinical Scientific Review Committee (CSRC), the Ohio State Cancer Institutional Review Board (OSU IRB 2015C0155), and with the 1964 Helsinki declaration and its later amendments.

Informed consent

The Ohio State Cancer Institutional Review Board (OSU IRB 2015C0155) approved the full waiver of the informed consent process due to the retrospective nature of the study.

References

  1. 1.
    Noone AM, Howlader N, Krapcho M et al (2018) SEER Cancer statistics review, 1975–2015. National Cancer Institute, BethesdaGoogle Scholar
  2. 2.
    Mayer EL, Burstein HJ (2007) Chemotherapy for metastatic breast cancer. Hematol Oncol Clin North Am 21:257–272.  https://doi.org/10.1016/j.hoc.2007.03.001 CrossRefPubMedGoogle Scholar
  3. 3.
    Genetech USA Inc (2016) Xeloda [package insert]Google Scholar
  4. 4.
    Schellens JHM (2007) Capecitabine. Oncologist 12:152–155.  https://doi.org/10.1634/theoncologist.12-2-152 CrossRefPubMedGoogle Scholar
  5. 5.
    Fumoleau P, Largillier R, Clippe C et al (2004) Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 40:536–542.  https://doi.org/10.1016/j.ejca.2003.11.007 CrossRefPubMedGoogle Scholar
  6. 6.
    Reichardt P, Von Minckwitz G, Thuss-Patience PC, et al (2003) Multicenter phase II study of oral capecitabine (Xeloda(")) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy. Ann Oncol 14:1227–1233.  https://doi.org/10.1093/annonc/mdg346 CrossRefGoogle Scholar
  7. 7.
    Oshaughnessy JA, Blum J, Moiseyenko V et al (2001) Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12:1247–1254CrossRefGoogle Scholar
  8. 8.
    Bajetta E, Procopio G, Celio L et al (2005) Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol 23:2155–2161.  https://doi.org/10.1200/JCO.2005.02.167 CrossRefPubMedGoogle Scholar
  9. 9.
    Thomas ES, Gomez HL, Li RK et al (2007) Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 25:5210–5217.  https://doi.org/10.1200/JCO.2007.12.6557 CrossRefPubMedGoogle Scholar
  10. 10.
    Geyer CE, Forster J, Lindquist D et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743.  https://doi.org/10.1056/NEJMoa064320 CrossRefPubMedGoogle Scholar
  11. 11.
    Bartsch R, Wenzel C, Altorjai G et al (2007) Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol 25:3853–3858.  https://doi.org/10.1200/JCO.2007.11.9776 CrossRefPubMedGoogle Scholar
  12. 12.
    Scheithauer W, Kornek GV, Raderer M et al (2003) Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 21:1307–1312.  https://doi.org/10.1200/JCO.2003.09.016 CrossRefPubMedGoogle Scholar
  13. 13.
    Traina TA, Theodoulou M, Feigin K et al (2008) Phase I study of a novel capecitabine schedule based on the Norton-Simon mathematical model in patients with metastatic breast cancer. J Clin Oncol 26:1797–1802.  https://doi.org/10.1200/JCO.2007.13.8388 CrossRefPubMedGoogle Scholar
  14. 14.
    Gajria D, Feigin K, Tan LK et al (2011) Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer. Cancer 117:4125–4131.  https://doi.org/10.1002/cncr.25992 CrossRefPubMedGoogle Scholar
  15. 15.
    Hennessy BT, Gauthier AM, Michaud LB et al (2005) Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer center and a review of capecitabine toxicity in the literature. Ann Oncol 16:1289–1296.  https://doi.org/10.1093/annonc/mdi253 CrossRefPubMedGoogle Scholar
  16. 16.
    Zielinski C, Gralow J, Martin M (2010) Optimising the dose of capecitabine in metastatic breast cancer: confused, clarified or confirmed? Ann Oncol 21:2145–2152.  https://doi.org/10.1093/annonc/mdq069 CrossRefPubMedGoogle Scholar
  17. 17.
    Nishijima TF, Suzuki M, Muss HB (2016) A comparison of toxicity profiles between the lower and standard dose capecitabine in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 156:227–236.  https://doi.org/10.1007/s10549-016-3756-5 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Traina TA, Dugan U, Higgins B et al (2010) Optimizing chemotherapy dose and schedule by Norton-Simon mathematical modeling. Breast Dis 31:7–18.  https://doi.org/10.3233/BD-2009-0290 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cadoo KA, Gajria D, Suh E et al (2016) Decreased gastrointestinal toxicity associated with a novel capecitabine schedule (7 days on and 7 days off): a systematic review. NPJ Breast Cancer 2:16006.  https://doi.org/10.1038/npjbcancer.2016.6 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Anupama Suresh
    • 1
    • 2
  • Akannsha Ganju
    • 1
    • 2
  • Evan Morgan
    • 1
    • 2
  • Marilly Palettas
    • 3
  • Julie A. Stephens
    • 3
  • Joseph Liu
    • 1
    • 2
  • Michael Berger
    • 1
    • 4
  • Craig Vargo
    • 1
    • 4
  • Anne Noonan
    • 1
    • 2
  • Raquel Reinbolt
    • 1
    • 2
  • Mathew Cherian
    • 1
    • 2
  • Jeffrey VanDeusen
    • 1
    • 2
  • Sagar Sardesai
    • 1
    • 2
  • Robert Wesolowski
    • 1
    • 2
  • Daniel G. Stover
    • 1
    • 2
  • Maryam Lustberg
    • 1
    • 2
  • Bhuvaneswari Ramaswamy
    • 1
    • 2
  • Nicole Williams
    • 1
    • 2
    • 5
    Email author
  1. 1.Stefanie Spielman Comprehensive Breast CenterThe Ohio State UniversityColumbusUSA
  2. 2.Division of Medical Oncology, Comprehensive Cancer CenterThe Ohio State University Medical CenterColumbusUSA
  3. 3.Department of Biomedical Informatics, Center for BiostatisticsThe Ohio State UniversityColumbusUSA
  4. 4.Pharmacy Department, Stefanie Spielman Comprehensive Breast CenterThe Ohio State UniversityColumbusUSA
  5. 5.Division of Medical OncologyThe Ohio State University Wexner Medical CenterColumbusUSA

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