Current Breast Cancer Reports

, Volume 4, Issue 1, pp 22–29

The Role of Capecitabine in Early Stage Breast Cancer

Systemic Therapy (J O’Shaughnessy, Section Editor)


Adjuvant systemic therapy is partly responsible for the decrease in breast cancer mortality we have seen over the past two decades. Hormonal therapy and combination chemotherapy based on anthracyclines and taxanes represent the best current approach for early breast cancer patients. Primary as well as secondary development of resistance represents the major challenges to improve our results. Major benefits have been achieved as we recognized populations with particular molecular abnormalities (HER2 positive) and applied specific targeted agents (trastuzumab). However, the addition of other traditional chemotherapy agents has remained a challenge. With consistent data both as a single agent and as part of combinations in the treatment of advanced disease, capecitabine is being explored in over 20,000 early breast cancer patients currently participating in clinical trials. In this review, we discuss the available evidence for the incorporation of capecitabine in the (neo)-adjuvant treatment of patients with breast cancer.


Early stage breast cancer Adjuvant chemotherapy Neo-adjuvant chemotherapy Capecitabine Clinical trials 


Papers of particular interest, published recently, have been highlighted as: • Of Importance

  1. 1.
    Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998; 352:930–942.Google Scholar
  2. 2.
    American Cancer Society. Cancer Facts & Figures 2011. Atlanta, American Cancer Society, 2011.Google Scholar
  3. 3.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Valero V, Slamon DJ, Eiermann W, et al. Efficacy results of node-negative HER2-amplified breast cancer subset from BCIRG 006 study: A phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin, and trastuzumab (TCH). J Clin Oncol 29: 2011 (suppl; abstract 553)Google Scholar
  7. 7.
    Stockler MR, Sourjina T, Grimison P, et al. A randomized trial of capecitabine (C) given intermittently (IC) rather than continuously (CC) compared to classical CMF as first-line chemotherapy for advanced breast cancer (ABC). J Clin Oncol 2007; 25:39s (Abstract 1031).Google Scholar
  8. 8.
    Zielinski C, Gralow J, Martin M. Optimising the dose of capecitabine in metastatic breast cancer: confused, clarified or confirmed? Ann Oncol. 2010;11:2145–52.CrossRefGoogle Scholar
  9. 9.
    O’Shaughnessy J, Miles D, Vukelja S, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002;20:2812–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Miles D, Vukelja S, Moiseyenko V, et al. Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial. Clin Breast Cancer. 2004;5:273–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Batista N, Perez-Manga G, Constela M, et al. Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Br J Cancer. 2004;90:1740–6.PubMedGoogle Scholar
  12. 12.
    Gradishar W, Meza LA, Amin B, et al. Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study. J Clin Oncol. 2004;22:2321–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Ahn JH, Kim SB, Ahn SH, et al. Phase II study of capecitabine and vinorelbine in anthracycline and taxane pretreated breast cancer patients: Final results. Proc Am Soc Clin Oncol 2003; 22:54 (Abstract 216).Google Scholar
  14. 14.
    Venturini M, Durando A, Garrone O, et al. Capecitabine in combination with docetaxel and epirubicin in patients with previously untreated, advanced breast carcinoma. Cancer. 2003;97:1174–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Sawada N, Ishikawa T, Fukase Y, et al. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res. 1998;4:1013–9.PubMedGoogle Scholar
  16. 16.
    Steger GG, Greil R, Jakesz R, et al. Pathologic complete response (pCR) in patient subgroups: An analysis of ABCSG-24, a phase III, randomized study of anthracycline- and taxane-based neo-adjuvant therapy with or without capecitabine in early breast cancer. J Clin Oncol 2010; 28:15s (suppl; abstract 530).Google Scholar
  17. 17.
    Steger GG, Greil R, Jakesz, et al. ABCSG-24: Efficacy of anthracycline and taxane-based neo-adjuvant therapy +/− capecitabine in triple-negative early breast cancer. Ann Oncol 2010; 21 (suppl 8)(Abstract 216).Google Scholar
  18. 18.
    Steger GG, Greil R, Jakesz R, et al. Final Results of ABCSG-24, a Randomized Phase III Study Comparing Epirubicin, Docetaxel, and Capecitabine (EDC) to Epirubicin and Docetaxel (ED) as Neo-adjuvant Treatment for Early Breast Cancer and Comparing ED/EDC+ Trastuzumab (T) to ED/EDC as Neo-adjuvant Treatment for Early HER-2 Positive Breast Cancer. Cancer Res 2009; 69 (Suppl 24): abstract 1081.Google Scholar
  19. 19.
    Lee KS, Ro J, Nam BH, et al. A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer. Breast Cancer Res Treat. 2008;109:481–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Untch M, Rezai M, Loibl S, et al. Neo-adjuvant Treatment With Trastuzumab in HER2-Positive Breast Cancer: Results From the GeparQuattro Study. J Clin Oncol. 2010;2024:31.Google Scholar
  21. 21.
    Gunter von Minckwitz G, Rezai M, Sibylle Loibl S, et al. Capecitabine in Addition to Anthracycline- and Taxane-Based Neo-adjuvant Treatment in Patients With Primary Breast Cancer: Phase III GeparQuattro Study. J Clin Oncol 2010:2015–2023.Google Scholar
  22. 22.
    Berton-Rigaud D, H. Roché, F. Penault-Llorca, et al. Benefit of neo-adjuvant capecitabine + epirubicin + cyclophosphamide (CEX) versus 5-FU + epirubicin + cyclophosphamide (FEC) for operable breast cancer (BC) followed by adjuvant docetaxel (T). J Clin Oncol 2008; 26: (abstract 598).Google Scholar
  23. 23.
    Jinno H, Sakata M, Hayashida T, et al. A phase II trial of capecitabine and docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer. Ann Oncol. 2010;21(6):1262–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Wildiers H, Neven P, Christiaens MR, et al. Neo-adjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer. Ann Oncol. 2011;22(3):588–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Perez EA, Hillman DW, Dentchev T, et al. North Central Cancer Treatment Group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer. Ann Oncol. 2010;2:269–74.CrossRefGoogle Scholar
  26. 26.
    Greil R, Moik M, Reitsamer R, et al. Neo-adjuvant bevacizumab, docetaxel and capecitabine combination therapy for HER2/neu-negative invasive breast cancer: Efficacy and safety in a phase II pilot study. Eur J Surg Oncol. 2009;35:1048–54.PubMedCrossRefGoogle Scholar
  27. 27.
    Ro J, Myung SK, Berton-Rigaud D, et al. The addition of capecitabine to neo-adjuvant chemotherapy for early breast cancer (EBC): a review of clinical study data. Eur J Cancer Suppls 2010; 8:72 (Abstract 48).Google Scholar
  28. 28.
    von Minckwitz G, M. Untch, E. Nueesch, et al. Impact of treatment characteristics on response of different breast cancer subtypes: Pooled multilayer analysis of the German neo-adjuvant chemotherapy trials. J Clin Oncol 2010; 28:15s (suppl; abstract 501).Google Scholar
  29. 29.
    • Muss HB, Berry DA, Cirrincione CT, et al. N Engl J Med 2009, 360:2055–65. This article describes a well-conducted clinical trial in a subgroup of elderly patients historically poorly represented in most adjuvant trials. PubMedCrossRefGoogle Scholar
  30. 30.
    • Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, et al. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol 2009; 12:1145–51. This is the first trial to demonstrate a benefit for the incorporation of capecitabine to a standard anthracycline-taxane adjuvant regimen.CrossRefGoogle Scholar
  31. 31.
    Kurosumi M, Tabei T, Suemasu K, et al. Enhancement of immunohistochemical reactivity for thymidine phosphorylase in breast carcinoma cells after administration of docetaxel as a neo-adjuvant chemotherapy in advanced breast cancer patients. Oncol Rep. 2000;7(5):945–8.PubMedGoogle Scholar
  32. 32.
    Fujimoto-Ouchi K, Tanaka Y, Tominaga T. Clin Cancer Res. 2001;7:1079–8.PubMedGoogle Scholar
  33. 33.
    Joensuu H, P. Kellokumpu-Lehtinen, R. Huovinen, et al. Integration of capecitabine (X) into adjuvant therapy comprising docetaxel (T) followed by 5-FU, epirubicin, and cyclophosphamide (CEF): Efficacy in patients with triple-negative breast cancer (BC). J Clin Oncol 2010; 28:15s, (suppl; abstract 531).Google Scholar
  34. 34.
    O’Shaughnessy J, Paul D, Stokoe C, et al. First Efficacy Results of a Randomized, Open-Label, Phase III Study of Adjuvant Doxorubicin Plus Cyclophosphamide, Followed by Docetaxel with or without Capecitabine, in High-Risk Early Breast Cancer. Cancer Res 2010; 70 (Suppl 24): abstract S4-2.Google Scholar
  35. 35.
    Shao Z, Huang B, Zhang J, et al. First interim analysis of a randomized trial comparing capecitabine/epirubicin/cyclophosphamide (XEC) vs 5-FU/epirubicin/cyclophosphamide (FEC) as adjuvant therapy for medium- or high-risk early breast cancer (EBC). Eur J Cancer Suppls 2010; 8:64 (Abstract 22).Google Scholar
  36. 36.
    Martin M, et al. First Safety Data from a Randomised Phase III Trial Comparing Adjuvant Epirubicin-Cyclophosphamide followed by Docetaxel (EC followed by T) vs. ET followed by Capecitabine (X) in Node-Positive Operable Breast Cancer (BC). Presented at St. Gallen Oncology Conference 'Primary Therapy of Early Breast Cancer’ March 13, 2009. Poster 0145.Google Scholar
  37. 37.
    Mulders M, Vingerhoets A, Breed W. The impact of cancer and chemotherapy: perceptual similarities and differences between cancer patients, nurses and physicians. Eur J Oncol Nurs. 2008;12(2):97–102.PubMedCrossRefGoogle Scholar
  38. 38.
    Lemieux J, Maunsell E, Provencher L, et al. Chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: a literature review. Psychooncology. 2008;17(4):317–28.PubMedCrossRefGoogle Scholar
  39. 39.
    Shin HW, Noh DY, Lee ES, et al. Correlates of existential well-being and their association with health-related quality of life in breast cancer survivors compared with the general population. Breast Cancer Res Treat. 2009;118(1):139–50.PubMedCrossRefGoogle Scholar
  40. 40.
    Macquart-Moulin G, Viens P, Bouscary ML, et al. Discordance between physicians’ estimations and breast cancer patients’ self-assessment of side-effects of chemotherapy: an issue for quality of care. Br J Cancer. 1997;76(12):1640–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Möbus V, Conrad, A. Schneeweis, et al. Gain study: A phase III trial to compare ETC versus EC-TX and ibandronate versus observation in patients with node-positive primary breast cancer. J Clin Oncol 2009; 27:15s, (suppl; abstract 568).Google Scholar
  42. 42.
    Reimer T, Nitz U, Potenberg J, et al. ICE Study: A prospective, multi-centre, controlled, open-label, randomized phase III trial of ibandronate (I) with or without capecitabine (X) in elderly patients (pts) with early breast cancer (GBG 32). Eur J Cancer Suppls 2009; 7:215 (Abstract O-4003).Google Scholar
  43. 43.
    Sledge G, Miller K, Sohl J, et al. Safety and efficacy of capecitabine plus bevacizumab as first line in metastatic breast cancer. J Clin Oncol 2007; 25(18), Abstract 1013.Google Scholar
  44. 44.
    Rugo H, Roche H, Thomas E, et al. Ixabepilone plus capecitabine vs. capecitabine in patients with triple negative tumors: a pooled analysis of patients from two large phase III clinical studies. Cancer Res 2008; 68 (Suppl 22): abstract 3057.Google Scholar
  45. 45.
    Steger GG, Barrios CH, O’Shaughnessy J, et al. Review of Capecitabine for the Treatment of Triple-Negative Early Breast Cancer. Cancer Res 2010; 70 (Suppl 24): abstract PD01-03.Google Scholar
  46. 46.
    Lluch A, Torrecillas L, Barrios CH, et al. CIBOMA/2004–01: a randomised phase III trial assessing adjuvant capecitabine maintenance therapy after standard chemotherapy for triple-negative early breast cancer. Eur J Cancer Suppls 2009; 7:304 (Abstract P-5150).Google Scholar
  47. 47.
    Lluch A, Gómez H, Ruiz-Borrego M, et al. First safety data from a randomized phase III (CIBOMA 2004–01 / GEICAM 2003–11) trial assessing adjuvant capecitabine maintenance therapy after standard chemotherapy for triple-negative early breast cancer. Cancer Res 2010; 70 (Suppl 24): abstract P5-1015.Google Scholar
  48. 48.
    Poole C, Barrios C, O’Shaughnessy J, et al. Ongoing Evaluation of Capecitabine-Based Therapy in Early Breast Cancer (EBC). Cancer Res 2010; 70 (Suppl 24): abstract P5-1011.Google Scholar
  49. 49.; identifier: NCT00301925.
  50. 50.; identifier: NCT00433589.

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.PUCRS School of MedicinePorto AlegreBrazil

Personalised recommendations