Cancer Treatment Reviews
Volume 35, Issue 7 , Pages 582-589 , November 2009

Contemporary issues and the potential uses of capecitabine in metastatic breast cancer

  • Peter Barrett-Lee

      Affiliations

    • Velindre Cancer Centre, Velindre Road, Cardiff CF14 2TL, UK
    • Tel.: +44 2920 316914; fax: +44 2920 316267.
  • ,
  • François-Clément Bidard

      Affiliations

    • Institut Curie Hospital, 26 rue d’Ulm, Paris 75248, France
  • ,
  • Jean-Yves Pierga

      Affiliations

    • Institut Curie Hospital, 26 rue d’Ulm, Paris 75248, France
    • Université Paris Descartes,12, rue de l’Ecole de Médecine, 75270 Paris Cedex 06, France
    • Corresponding Author InformationCorresponding author. Address: Institut Curie Hospital, 26 rue d’Ulm, Paris 75248, France. Tel.: +33 1 4432 4207; fax: +33 1 53104041.

Received 26 March 2009 ,Revised 10 June 2009 ,Accepted 12 June 2009.

References 

  1. 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(18S):1031
  2. 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;20:2812–2823
  3. Pegram M, Hsu S, Lewis G, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene. 1999;18:2241–2251
  4. Fujimoto-Ouchi K, Sekiguchi F, Tanaka Y. Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine/5′-dFUrd in human breast cancer models. Cancer Chemother Pharmacol. 2002;49:211–216
  5. Jahanzeb M, Mortimer JE, Yunus F, et al. Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2(+) metastatic breast cancer. Oncologist. 2002;7:410–417
  6. Burstein HJ, Kuter I, Campos SM, et al. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2001;19:2722–2730
  7. Burstein HJ, Harris LN, Marcom PK, et al. Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. J Clin Oncol. 2003;21:2889–2895
  8. Suzuki Y, Tokuda Y, Saito Y, et al. Combination of trastuzumab and vinorelbine in metastatic breast cancer. Jpn J Clin Oncol. 2003;33:514–517
  9. Chan A, Martin M, Untch M, et al. Navelbine herceptin project. Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial. Br J Cancer. 2006;95:788–793
  10. Burstein HJ, Keshaviah A, Baron AD, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007;110:965–972
  11. Yoshidome K, Imabun S, Nakahara M, et al. Case report of advanced breast cancer responding to capecitabine and trastuzumab combination therapy. Gan To Kagaku Ryoho. 2006;33:1453–1456
  12. Marutaka M, Suguri T, Miyake H, et al. A paclitaxel-resistant case of recurrent breast cancer responded to combination therapy of capecitabine and trastuzumab. Gan To Kagaku Ryoho. 2005;32:2137–2139
  13. Ardavanis A, Tryfonopoulos D, Orfanos G, et al. Safety and efficacy of trastuzumab every 3 weeks combined with cytotoxic chemotherapy in patients with HER2-positive recurrent breast cancer: findings from a case series. Onkologie. 2005;28:558–564
  14. Bangemann N, Kuhle A, Ebert A, et al. Capecitabine combined with trastuzumab in the therapy of intensively pretreated HER2-overexpressing metastatic breast cancer (MBC). Ann Oncol. 2000;11(Suppl. 4):143a
  15. Xu L, Song S, Zhu J, et al. Capecitabine (X)+trastuzumab (H) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC): phase II trial results. Breast Cancer Res Treat. 2006;100(Suppl. 1):S102;[abstract 2065]
  16. Yamamoto D, Iwase S, Kitamura K, et al. A phase II study of trastuzumab and capecitabine for patients with HER2-overexpressing metastatic breast cancer: Japan breast cancer research network (JBCRN) 00 trial. Cancer Chemother Pharmacol. 2008;61:509–514
  17. Schaller G, Fuchs I, Gonsch T, et al. Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol. 2007;25:3246–3250
  18. Bartsch R, Wenzel C, Altorjai G, et al. Capecitabine and trastuzumab in heavily pretreated patients with metastatic breast cancer. J Clin Oncol. 2007;25:3853–3858
  19. Ishida T, Kiba T, Takeda M, et al. Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 overexpressing metastatic breast cancer resistant to both anthracyclines and taxanes. Cancer Chemother Pharmacol. 2009;64:361–369
  20. von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German breast group 26/breast international group 03–05 study. J Clin Oncol. 2009;27:1999–2006
  21. Wardley A, Antón-Torres A, Pivot X, et al. Trastuzumab plus docetaxel with or without capecitabine as first-line therapy for HER2-positive locally advanced or metastatic breast cancer: a randomised phase II study. Eur J Cancer Suppl. 2008;6:109;[abstract 209]
  22. Osako T, Ito Y, Takahashi S, et al. Efficacy and safety of trastuzumab plus capecitabine in heavily pretreated patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2008;62:159–164
  23. Esteva FJ, Valero V, Booser D, et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:1800–1808
  24. Moisa C, Kolinsky K, Zhang YE, et al. Activity of capecitabine (C), docetaxel (D) doublets with, without trastuzumab (T) in a breast cancer xenograft model. Eur J Cancer Suppl. 2007;5:187;[abstract 2012]
  25. Chan A, Ganju V, Becquart D, et al. Multinational international phase II study of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination in HER2-positive metastatic breast cancer (MBC): updated results with longer follow-up. Cancer Res. 2009;69(Suppl.):253s;[abstract 3151]
  26. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–2743
  27. GlaxoSmithKline. Tyverb® US prescribing information. August 2007.
  28. Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112:533–543
  29. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–2676
  30. Miles D, Chan A, Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol. 2008;26(18S):1088s;[LBA1011]
  31. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–799
  32. Sledge G, Miller K, Moisa C, et al. Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer. J Clin Oncol. 2007;25(18S):1013
  33. Perez EA, Hillman DW, Kugler JW, 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. Breast Cancer Res Treat. 2006;100(Suppl. 1):S104;[abstract 2069]
  34. Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol. 2009;27(15S):42s;[abstract 1005]
  35. Tosoni A, Ermani M, Brandes AA. The pathogenesis and treatment of brain metastases: a comprehensive review. Crit Rev Oncol Hematol. 2004;52:199–215
  36. Aragon-Ching JB, Zujewski JA. CNS metastasis: an old problem in a new guise. Clin Cancer Res. 2007;13:1644–1647
  37. Gabos Z, Sinha R, Hanson J, et al. Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol. 2006;24:5658–5663
  38. Eichler AF, Kuter I, Ryan P, et al. Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer. 2008;112:2359–2367
  39. Weitzen R, Zach L, Kaufman B, et al. High incidence of brain metastases (BM) in patients on trastuzumab (H) for advanced breast cancer. J Clin Oncol. 2002;21(18S):1936
  40. Wardley AM, Danson S, Clayton AJ, et al. High incidence of brain metastases in patients treated with trastuzumab for metastatic breast cancer at a large cancer center. J Clin Oncol. 2002;21(18S):241
  41. Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972–2977
  42. Clayton AJ, Danson S, Jolly S, et al. Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer. 2004;91:639–643
  43. Pestalozzi BC, Zahrieh D, Price KN, et al. International breast cancer study group (IBCSG). Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the international breast cancer study group (IBCSG). Ann Oncol. 2006;17:935–944
  44. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–792
  45. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol. 2005;23:2114–2116
  46. Bartsch R, Rottendusser A, Wenzel C, et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol. 2007;85:311–317
  47. Dawood SS, Broglio K, Esteva FJ, et al. Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol. 2008;19:1242–1248
  48. Church DN, Modgil R, Guglani S, et al. Extended survival in women receiving trastuzumab for brain metastases from HER2 positive metastatic breast cancer. Am J Clin Oncol. 2008;31:250–254
  49. Pinder MC. Trastuzumab treatment and the risk of central nervous system (CNS) metastases. J Clin Oncol. 2007;25(18S):1018
  50. Park IH, Ro J, Lee KS, et al. Trastuzumab treatment beyond progression in HER2-positive metastatic breast cancer. Ann Oncol. 2009;20:56–62
  51. Lower EE, Drosick DR, Blau R, et al. Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer. 2003;4:114–119
  52. Pardridge WM. The blood–brain barrier: bottleneck in brain drug development. NeuroRx. 2005;2:3–14
  53. In:  McEvoy GK editors. Capecitabine. AHFS drug information. Bethesda, MD: American Society of Health-System Pharmacists; 2002;p. 916–21
  54. Heier MS, Heintz R, Fossa SD. Passage of 5′-dFUrd and its metabolites 5-FU and 5-FUH2 to CSF in a clinical phase 1 study. Acta Neurol Scand. 1986;74:240–244
  55. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004;22:3608–3617
  56. Rosner D, Nemoto T, Lane WW. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer. 1986;58:832–839
  57. Boogerd W, Dalesio O, Bais EM, et al. Response of brain metastases from breast cancer to systemic chemotherapy. Cancer. 1992;69:972–980
  58. Boogerd W, van den Bent MJ, Koehler PJ, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer. 2004;40:2726–2733
  59. Vick NA, Khandekar JD, Bigner DD. Chemotherapy of brain tumors. Arch Neurol. 1977;34:523–526
  60. Chang EL, Lo S. Diagnosis and management of central nervous system metastases from breast cancer. Oncologist. 2003;8:398–410
  61. Arif S, Barrett-Lee PJ, Jordan C. The incidence and treatment outcome after radiotherapy for brain metastases in HER-2-positive metastatic breast cancer patients treated with trastuzumab. Clin Oncol. 2006;18:719–724
  62. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363:1665–1672
  63. Videnovic A, Semenov I, Chua-Adajar R, et al. Capecitabine-induced multifocal leukoencephalopathy: a report of five cases. Neurology. 2005;65:1792–1794
  64. Niemann B, Rochlitz C, Herrmann R, et al. Toxic encephalopathy induced by capecitabine. Oncology. 2004;66:331–335
  65. Couch LS, Groteluschen DL, Stewart JA, et al. Capecitabine-related neurotoxicity presenting as trismus. Clin Colorectal Cancer. 2003;3:121–123
  66. Renouf D, Gill S. Capecitabine-induced cerebellar toxicity. Clin Colorectal Cancer. 2006;6:70–71
  67. Formica V, Leary A, Cunningham D, et al. 5-Fluorouracil can cross brain–blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma. Cancer Chemother Pharmacol. 2006;58:276–278
  68. Mukesh M, Murray P. Cerebellar toxicity with capecitabine in a patient with metastatic breast cancer. Clin Oncol (R Coll Radiol). 2008;20:382–383
  69. Tamai I, Tsuji A. Transporter-mediated permeation of drugs across the blood–brain barrier. J Pharm Sci. 2000;89:1371–1388
  70. Bourke RS, West CR, Chheda G, et al. Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res. 1973;33:1735–1746
  71. Mata JF, Garcia-Manteiga JM, Lostao MP, et al. Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5′-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug. Mol Pharmacol. 2001;59:1542–1548
  72. Anderson CM, Xiong W, Young JD, et al. Demonstration of the existence of mRNAs encoding N1/cif and N2/cit sodium/nucleoside cotransporters in rat brain. Brain Res Mol Brain Res. 1996;42:358–361
  73. Rivera E, Meyers C, Groves M, et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer. 2006;107:1348–1354
  74. Christodoulou C, Bafaloukos D, Kosmidis P, et al. Hellenic cooperative oncology group. Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Ann Oncol. 2001;12:249–254
  75. Abrey LE, Olson JD, Raizer JJ, et al. A phase II trial of temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol. 2001;53:259–265
  76. Antonadou D, Paraskevaidis M, Sarris G, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002;20:3644–3650
  77. Kouvaris JR, Miliadou A, Kouloulias VE, et al. Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors. Onkologie. 2007;30:361–366
  78. Trudeau ME, Crump M, Charpentier D, et al. Temozolomide in metastatic breast cancer (MBC): a phase II trial of the national cancer institute of Canada – clinical trials group (NCIC – CTG). Ann Oncol. 2006;17:952–956
  79. Ceresoli GL, Cappuzzo F, Gregorc V, et al. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol. 2004;15:1042–1047
  80. Lin NU, Dieras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009;15:1452–1459
  81. Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008;26:1993–1999
  82. Ekenel M, Hormigo AM, Peak S, et al. Capecitabine therapy of central nervous system metastases from breast cancer. J Neurooncol. 2007;85:223–227
  83. Hikino H, Yamada T, Johbara K, et al. Potential role of chemo-radiation with oral capecitabine in a breast cancer patient with central nervous system relapse. Breast. 2006;15:97–99
  84. Wang ML, Yung WK, Royce ME, et al. Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer. Am J Clin Oncol. 2001;24:421–424
  85. Giglio P, Tremont-Lukats IW, Groves MD. Response of neoplastic meningitis from solid tumors to oral capecitabine. J Neurooncol. 2003;65:167–172Erratum in: J Neurooncol 2004;68:295
  86. Siegelmann-Danieli N, Stein M, Bar-Ziv J. Complete response of brain metastases originating in breast cancer to capecitabine therapy. Isr Med Assoc J. 2003;5:833–834
  87. Church DN, Bahl A, Jones A, et al. HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab – a case report. J Neurooncol. 2006;79:289–292
  88. Chargari C, Kirova YM, Diéras V, et al. Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients. J Neurooncol. 2009;93:379–384
  89. Carmona-Bayonas A. Concurrent radiotherapy and capecitabine, followed by high-dose methotrexate consolidation, provided effective palliation in a patient with leptomeningeal metastases from breast cancer. Ann Oncol. 2007;18:199–200
  90. Tham YL, Hinckley L, Teh BS, et al. Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report. Clin Breast Cancer. 2006;7:164–166
  91. Rogers LR, Remer SE, Tejwani S. Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy. Neuro Oncol. 2004;6:63–64
  92. Fabi A, Vidiri A, Ferretti G, et al. Dramatic regression of multiple brain metastases from breast cancer with capecitabine: another arrow at the bow?. Cancer Invest. 2006;24:466–468
  93. Shigekawa T, Takeuchi H, Misumi M, et al. Successful treatment of leptomeningeal metastases from breast cancer using the combination of trastuzumab and capecitabine: a case report. Breast Cancer. 2009;16:88–92
  94. Glynne-Jones R, Dunst J, Sebag-Montefiore D. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been?. Ann Oncol. 2006;17:361–371
  95. Gaui MF, Amorim G, Arcuri RA, et al. A phase II study of second-line neoadjuvant chemotherapy with capecitabine and radiation therapy for anthracycline-resistant locally advanced breast cancer. Am J Clin Oncol. 2007;30:78–81Erratum in: Am J Clin Oncol 2007;30:331
  96. Di Bartolomeo M, Bajetta E, Beretta E, et al. Radiosensitization with capecitabine after curative surgery for rectal cancer. Proc Am Soc Clin Oncol. 2003;22:314;[abstract 1262]
  97. Sawada N, Ishikawa T, Sekiguchi F, et al. X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res. 1999;5:2948–2953
  98. Blanquicett C, Gillespie GY, Nabors LB, et al. Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002;1:1139–1145
  99. Blanquicett C, Saif MW, Buchsbaum DJ, et al. Antitumor efficacy of capecitabine and celecoxib in irradiated and lead-shielded, contralateral human BxPC-3 pancreatic cancer xenografts: clinical implications of abscopal effects. Clin Cancer Res. 2005;11:8773–8781
  100. Muss HB, Case LD, Richards F, et al. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The piedmont oncology association. N Engl J Med. 1991;325:1342–1348
  101. Coates A, Stockler M, Wilcken N. Controversies in metastatic breast cancer: optimal duration of chemotherapy. Am Soc Clin Oncol Educ Book. 2003;119–121
  102. Gennari A, Amadori D, De Lena M, et al. Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer. J Clin Oncol. 2006;24:3912–3918
  103. Alba E, Ruiz-Borrego M, Martín M, et al. Multicenter phase III trial to evaluate pegylated liposomal doxorubicin as maintenance chemotherapy (CT) vs observation, after first-line CT with sequential doxorubicin and docetaxel (A–T) in metastatic breast cancer (MBC). GEICAM 2000–01 study. Eur J Cancer Suppl. 2008;19(Suppl. 8):viii66;[abstract 145P]
  104. Joensuu H, Kellokumpu-Lehtinen P, Huovinen R, et al. for the Finnish Breast Cancer Group Significant improvement in recurrence-free survival (RFS) when capecitabine (X) is integrated into docetaxel (T)5-FU+epirubicin+cyclophosphamide (CEF) adjuvant therapy for high-risk early breast cancer (BC): interim analysis of the FinXX-trial. Cancer Res. 2009;69(Suppl.):3;[abstract 82]
  105. Tripathy D. Capecitabine in combination with novel targeted agents in the management of metastatic breast cancer: underlying rationale and results of clinical trials. Oncologist. 2007;12:375–389

PII: S0305-7372(09)00090-5

doi: 10.1016/j.ctrv.2009.06.003

Cancer Treatment Reviews
Volume 35, Issue 7 , Pages 582-589 , November 2009