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Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy

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Abstract

Purpose

Capecitabine has been studied as a radiosensitizer, and our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on event-free- (EFS) and overall survival (OS) in women with breast cancer (BC) with residual disease after neoadjuvant chemotherapy (NAC).

Methods/patients

In a retrospective study of women with BC who received adriamycin/taxane-based NAC from 2004–2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (n = 57) based on criteria used to select patients for capecitabine/RT. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage and age (< 50 or 50+ years). Differences in EFS, using STEEP criteria, and OS, using all-cause mortality, between those who received capecitabine/RT and controls were assessed.

Results

Of the 21 women who received capecitabine/RT, median age was 52 years. The majority were pathologic stage III (n = 15) and hormone receptor-positive/HER2-negative BC (n = 20). In those receiving capecitabine/RT, there were 9 events, compared with 14 events in clinical and 10 events in matched controls. Capecitabine/RT was associated with worse OS in clinical (HR 3.83 95% CI 1.12–13.11, p = 0.03) and matched controls (HR 3.71 95% CI 1.04–13.18, p = 0.04), after adjusting for clinical size, pathological stage and lymphovascular invasion. Capecitabine/RT was also associated with a trend towards worse EFS in clinical (HR 2.41 95% CI 0.86–6.74, p = 0.09) and matched controls (HR 2.68 95% CI 0.91–7.90, p = 0.07) after adjustment.

Conclusion

Concurrent capecitabine/RT after NAC is associated with worse survival and should be carefully considered in BC.

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Abbreviations

NAC:

Neoadjuvant chemotherapy

RT:

Radiation therapy

BC:

Breast cancer

TNBC:

Triple-negative breast cancer

pCR:

Pathological complete response

EFS:

Event-free survival

OS:

Overall survival

References

  1. Chaudry M, Lei X, Gonzalez-Angulo AM, et al. Recurrence and survival among breast cancer patients achieving a pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2015;153(2):417–23.

    Article  CAS  Google Scholar 

  2. Rustogi A, Budrukkar A, Dinshaw K, Jalali R. Management of locally advanced breast cancer: evolution and current practice. J Cancer Res Ther. 2005;1(1):21–30.

    Article  Google Scholar 

  3. Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998;34(8):1274–81.

    Article  CAS  Google Scholar 

  4. Walko CM, Lindley C. Capecitabine: a review. Clin Ther. 2005;27(1):23–44.

    Article  CAS  Google Scholar 

  5. Blum JL. Xeloda in the treatment of metastatic breast cancer. Oncology. 1999;57(Suppl 1):16–20.

    Article  CAS  Google Scholar 

  6. Wagstaff AJ, Ibbotson T, Goa KL. Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217–36.

    Article  CAS  Google Scholar 

  7. Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360(20):2055–65.

    Article  CAS  Google Scholar 

  8. Zhang ZC, Xu QN, Lin SL, Li XY. Capecitabine in combination with standard (neo) adjuvant regimens in early breast cancer: survival outcome from a meta-analysis of randomized controlled trials. PLoS One. 2016;11(10):e0164663.

    Article  CAS  Google Scholar 

  9. McGale P, Taylor C, Correa C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935):2127–35.

    Article  CAS  Google Scholar 

  10. Mandilaras V, Bouganim N, Spayne J, et al. Concurrent chemoradiotherapy for locally advanced breast cancer-time for a new paradigm? Curr Oncol (Toronto, Ont). 2015;22(1):25–32.

    Article  CAS  Google Scholar 

  11. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324(11):709–15.

    Article  CAS  Google Scholar 

  12. Zhu AX, Willett CG. Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer. Semin Radiat Oncol. 2003;13(4):454–68.

    Article  Google Scholar 

  13. Abrams MJ, Huber KE, Knisely JP, Chang BW, Russo SM, Saif MW. Capecitabine as a radiosensitizer in adjuvant chemoradiotherapy for pancreatic cancer: a retrospective study. Anticancer Res. 2015;35(12):6901–7.

    PubMed  CAS  Google Scholar 

  14. Yang YF, Cao XH, Bao CE, Wan X. Concurrent radiotherapy with oral fluoropyrimidine versus gemcitabine in locally advanced pancreatic cancer: a systematic review and meta-analysis. OncoTargets Ther. 2015;8:3315–22.

    CAS  Google Scholar 

  15. Rouesse J, de la Lande B, Bertheault-Cvitkovic F, et al. A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results. Int J Radiat Oncol Biol Phys. 2006;64(4):1072–80.

    Article  CAS  Google Scholar 

  16. Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S. American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract Am Soc Clin Oncol. 2010;6(4):195–7.

    Article  Google Scholar 

  17. Tchrakian N, Flanagan L, Harford J, Gannon JM, Quinn CM. New ASCO/CAP guideline recommendations for HER2 testing increase the proportion of reflex in situ hybridization tests and of HER2 positive breast cancers. Virchows Arch. 2016;468(2):207–11.

    Article  CAS  Google Scholar 

  18. Zhang C, Wang S, Israel HP, et al. Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy, surgery and radiotherapy. SpringerPlus. 2015;4:386.

    Article  Google Scholar 

  19. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  Google Scholar 

  20. Grossman SA, Ye X, Lesser G, et al. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res. 2011;17(16):5473–80.

    Article  CAS  Google Scholar 

  21. Hughes MA, Parisi M, Grossman S, Kleinberg L. Primary brain tumors treated with steroids and radiotherapy: low CD4 counts and risk of infection. Int J Radiat Oncol Biol Phys. 2005;62(5):1423–6.

    Article  CAS  Google Scholar 

  22. Wild AT, Herman JM, Dholakia AS, et al. Lymphocyte-sparing effect of stereotactic body radiation therapy in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2016;94(3):571–9.

    Article  Google Scholar 

  23. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127–32.

    Article  Google Scholar 

  24. Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, et al. Adjuvant capecitabine in combination with docetaxel, epirubicin, and cyclophosphamide for early breast cancer: the randomized clinical FinXX trial. JAMA Oncol. 2017;3(6):793–800.

    Article  Google Scholar 

  25. Martin M, Ruiz Simon A, Ruiz Borrego M, et al. Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 study. J Clin Oncol. 2015;33(32):3788–95.

    Article  CAS  Google Scholar 

  26. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–59.

    Article  CAS  Google Scholar 

  27. Shaughnessy JN, Meena RA, Dunlap NE, et al. Efficacy of concurrent chemoradiotherapy for patients with locally recurrent or advanced inoperable breast cancer. Clin Breast Cancer. 2015;15(2):135–42.

    Article  Google Scholar 

  28. Liu YL, Saraf A, Lee SM, et al. Lymphovascular invasion is an independent predictor of survival in breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2016;157(3):555–64.

    Article  CAS  Google Scholar 

  29. Davuluri R, Jiang W, Fang P, et al. Lymphocyte nadir and esophageal cancer survival outcomes after chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2017;99(1):128–35.

    Article  Google Scholar 

  30. Toledano A, Garaud P, Serin D, et al. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conserving surgery enhances late toxicities: long-term results of the ARCOSEIN multicenter randomized study. Int J Radiat Oncol Biol Phys. 2006;65(2):324–32.

    Article  CAS  Google Scholar 

  31. Ray-Coquard I, Cropet C, Van Glabbeke M, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69(13):5383–91.

    Article  CAS  Google Scholar 

  32. Printz C. Minority women more likely to develop aggressive breast cancer. Cancer. 2016;122(7):986–7.

    Article  Google Scholar 

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Funding

This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number KL2 TR000081. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. Y. L. Liu and C. Chin are co-first authors.

Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Y. L. Liu

  2. Department of Radiation Oncology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA

    C. Chin, B. Catanese & E. P. Connolly

  3. Department of Biostatistics, Columbia University School of Medicine, New York, NY, USA

    S. M. Lee & S. Zhan

  4. Department of Medical Oncology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA

    K. Kalinsky

Authors
  1. Y. L. Liu
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  2. C. Chin
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  4. S. M. Lee
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Corresponding author

Correspondence to E. P. Connolly.

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Conflict of interest

Author EC has received funding from Merck and has served as a consultant for Eisai. Author KK has served as a consultant for Lilly, Biotheranostics, Amgen, Eisai, and Novartis. All other authors report no declarations of interest.

Ethical approval

All research was conducted in accordance with CUMC IRB approved protocol (IRB #AAAJ8512).

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Informed consent was provided to all participants per protocol.

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Liu, Y.L., Chin, C., Catanese, B. et al. Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy. Clin Transl Oncol 20, 1280–1288 (2018). https://doi.org/10.1007/s12094-018-1859-7

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  • DOI: https://doi.org/10.1007/s12094-018-1859-7

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