Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 4, pp 913–919 | Cite as

All-oral combination of vinorelbine and capecitabine as first-line treatment in HER2/Neu-negative metastatic breast cancer

Original Article



To evaluate the efficacy and safety of an all-oral vinorelbine and capecitabine combination therapy in anthracycline- ± taxane-pretreated HER2/Neu-negative metastatic breast cancer (MBC).


A phase 2 trial including women >18 years with HER2/Neu-negative MBC previously exposed to anthracycline- ± taxane-based chemotherapy in the adjuvant or neoadjuvant setting. Enrolled patients received oral vinorelbine 60 mg/m2 on days 1 and 8 and oral capecitabine 1,000 mg/m2 twice daily on days 1–14 on a 3 weekly schedule. Patients with progressive disease after 3 cycles discontinued the study, while the remaining patients continued treatment for a maximum of 6 cycles.


From January 2007 to March 2011, 30 patients were enrolled in this study (median age 47 years). In the 28 evaluable patients, the overall response rate was 57.1 % (95 % CI 30–67 %), including 3 complete (10.7 %) and 13 partial (46.4 %) responses. Six (21.4 %) patients suffered from disease progression. With a median follow-up time of 13 months, the median time to disease progression was 8.6 months (95 % CI 6.2–10.6 months) and the median survival time was 27.2 months. Treatment-related adverse events were manageable, and no World Health Organization grade 4 toxicities were noted. Neutropenia observed in 6 (21.4 %) patients was the main grade 3 toxicity. Grade 3 nausea and vomiting were reported in 2 (7.1 %) and 3 (10.7 %) patients, respectively. Two (7.1 %) patients developed grade 3 hand and foot syndrome.


These results show that the combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for HER2/Neu-negative MBC patients pretreated with anthracyclines ± taxanes.


Oral therapy First-line chemotherapy Metastatic breast cancer HER2/Neu-negative 


Conflict of interest

None to disclose.


  1. 1.
    DeSantis C, Siegel R, Bandi P, Jemal A (2011) Breast cancer statistics, 2011. CA Cancer J Clin 61(6):409–418. doi: 10.3322/caac.20134 PubMedCrossRefGoogle Scholar
  2. 2.
    Althuis MD, Dozier JM, Anderson WF, Devesa SS, Brinton LA (2005) Global trends in breast cancer incidence and mortality 1973–1997. Int J Epidemiol 34(2):405–412. doi: 10.1093/ije/dyh414 PubMedCrossRefGoogle Scholar
  3. 3.
    Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150. doi: 10.1200/JCO.2005.05.2308 PubMedCrossRefGoogle Scholar
  4. 4.
    Finek J, Holubec L Jr, Svoboda T, Sefrhansova L, Pavlikova I, Votavova M, Sediva M, Filip S, Kozevnikova R, Kormunda S (2009) A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer. Anticancer Res 29(2):667–670PubMedGoogle Scholar
  5. 5.
    De Mattos-Arruda L, Cortes J (2012) Advances in first-line treatment for patients with HER-2+ metastatic breast cancer. Oncologist. doi: 10.1634/theoncologist.2011-0187 PubMedGoogle Scholar
  6. 6.
    Bedard PL, Di Leo A, Piccart-Gebhart MJ (2010) Taxanes: optimizing adjuvant chemotherapy for early-stage breast cancer. Nat Rev Clin Oncol 7(1):22–36. doi: 10.1038/nrclinonc.2009.186 PubMedCrossRefGoogle Scholar
  7. 7.
    Henderson IC (2011) Can we abandon anthracyclines for early breast cancer patients? Oncology (Williston Park) 25(2):115–124, 127Google Scholar
  8. 8.
    Jones A, O’Brien M, Sommer H, Nowara E, Welt A, Pienkowski T, Rolski J, Pham ML, Perraud K, Trillet-Lenoir V (2010) Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Cancer Chemother Pharmacol 65(4):755–763. doi: 10.1007/s00280-009-1081-y PubMedCrossRefGoogle Scholar
  9. 9.
    Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98. doi: 10.1200/JCO.2008.19.9844 PubMedCrossRefGoogle Scholar
  10. 10.
    Binet S, Fellous A, Lataste H, Krikorian A, Couzinier JP, Meininger V (1989) In situ analysis of the action of Navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16(2 Suppl 4):5–8PubMedGoogle Scholar
  11. 11.
    Saif MW, Katirtzoglou NA, Syrigos KN (2008) Capecitabine: an overview of the side effects and their management. Anticancer Drugs 19(5):447–464. doi: 10.1097/CAD.0b013e3282f945aa PubMedGoogle Scholar
  12. 12.
    Nole F, Crivellari D, Mattioli R, Pinotti G, Foa P, Verri E, Fougeray R, Brandely M, Goldhirsch A (2009) Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer. Cancer Chemother Pharmacol 64(4):673–680. doi: 10.1007/s00280-008-0915-3 PubMedCrossRefGoogle Scholar
  13. 13.
    Sawada N, Fujimoto-Ouchi F, Ishikawa T (2002) Antitumor activity of combination therapy with capecitabine plus vinorelbine, and capecitabine plus gemcitabine in human tumor xenograft models [abstract 5388]. Proc Am Assoc Cancer Res 43:1088aGoogle Scholar
  14. 14.
    Chan A, Verrill M (2009) Capecitabine and vinorelbine in metastatic breast cancer. Eur J Cancer 45(13):2253–2265. doi: 10.1016/j.ejca.2009.04.031 PubMedCrossRefGoogle Scholar
  15. 15.
    Cardoso F, Castiglione M (2009) Locally recurrent or metastatic breast cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 20(Suppl 4):15–18. doi: 10.1093/annonc/mdp115 PubMedGoogle Scholar
  16. 16.
    Cardoso F, Fallowfield L, Costa A, Castiglione M, Senkus E (2011) Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi25–vi30. doi: 10.1093/annonc/mdr372 PubMedCrossRefGoogle Scholar
  17. 17.
    Liu G, Franssen E, Fitch MI, Warner E (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15(1):110–115PubMedGoogle Scholar
  18. 18.
    Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C (2001) Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol 12(11):1643–1649PubMedCrossRefGoogle Scholar
  19. 19.
    Aapro M, Finek J (2012) Oral vinorelbine in metastatic breast cancer: a review of current clinical trial results. Cancer Treat Rev 38(2):120–126. doi: 10.1016/j.ctrv.2011.05.005 PubMedCrossRefGoogle Scholar
  20. 20.
    Estevez LG, Batista N, Sanchez-Rovira P, Velasco A, Provencio M, Leon A, Domine M, Cruz J, Rodriguez M (2008) A Phase II study of capecitabine and vinorelbine in patients with metastatic breast cancer pretreated with anthracyclines and taxanes. Clin Breast Cancer 8(2):149–154. doi: 10.3816/CBC.2008.n.015 PubMedCrossRefGoogle Scholar
  21. 21.
    Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47(1):207–214PubMedCrossRefGoogle Scholar
  22. 22.
    Mangino P, Taft B, Djulbegovic B (1997) Criteria for grading toxicity. In: Djulbegovic B, Sullivan DM (eds) Decision making in oncology: evidence-based management, 1st edn. Churchill Livingstone, New York, pp 454–468Google Scholar
  23. 23.
    Borner MM, Schoffski P, de Wit R, Caponigro F, Comella G, Sulkes A, Greim G, Peters GJ, van der Born K, Wanders J, de Boer RF, Martin C, Fumoleau P (2002) Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 38(3):349–358PubMedCrossRefGoogle Scholar
  24. 24.
    Lorusso V, Spada M, Giampaglia M, Misino A, Calabrese R, Latorre A, Monticelli G, Guida M, Sambiasi D, Colucci G (2006) Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC). A phase II study of the GOIM (Gruppo Oncologico dell’Italia Meridionale). Ann Oncol 17(Suppl 7):15–17. doi: 10.1093/annonc/mdl942 Google Scholar
  25. 25.
    Tubiana-Mathieu N, Bougnoux P, Becquart D, Chan A, Conte PF, Majois F, Espie M, Morand M, Vaissiere N, Villanova G (2009) All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial. Br J Cancer 101(2):232–237. doi: 10.1038/sj.bjc.6605156 PubMedCrossRefGoogle Scholar
  26. 26.
    Delcambre C, Veyret C, Levy C, Switsers O (2005) A phase I/II study of capecitabine combined with oral vinorelbine as first or second line therapy in locally advanced or metastatic breast cancer [abstract 1081]. Breast Cancer Res Treat 94:S67Google Scholar
  27. 27.
    Campone M, Dobrovolskaya N, Tjulandin S, Chen SC, Fourie SJ, Mefti F, Konstantinova M, Lefresne F, Meheust N, Jassem J (2011) Final results of a three-arm randomised phase II study of oral vinorelbine plus capecitabine versus oral vinorelbine and capecitabine in sequence versus docetaxel plus capecitabine in patients with metastatic breast cancer previously treated with anthracyclines. Abstract presented at the CTRC-AACR 2011 San Antonio Breast Cancer SymposiumGoogle Scholar
  28. 28.
    Gampenrieder SP, Bartsch R, Matzneller P, Pluschnig U, Dubsky P, Gnant MX, Zielinski CC, Steger GG (2010) Capecitabine and vinorelbine as an all-oral chemotherapy in HER2-negative locally advanced and metastatic breast cancer. Breast Care (Basel) 5(3):158–162. doi: 10.1159/000314214 CrossRefGoogle Scholar
  29. 29.
    Petrelli F, Barni S (2010) Oral vinorelbine: its role in advanced breast cancer pre-treated with anthracycline and taxane chemotherapies. Oncol Rev 4(1):61–69CrossRefGoogle Scholar
  30. 30.
    Rousseau F, Retornaz F, Joly F, Esterni B, Abadie-Lacourtoisie S, Fargeot P, Luporsi E, Servent V, Laguerre B, Brain E, Geneve J (2010) Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: a multicentre pilot study of the French geriatric oncology group (GERICO). Crit Rev Oncol Hematol 76(1):71–78. doi: 10.1016/j.critrevonc.2009.12.003 PubMedCrossRefGoogle Scholar
  31. 31.
    Findlay M, von Minckwitz G, Wardley A (2008) Effective oral chemotherapy for breast cancer: pillars of strength. Ann Oncol 19(2):212–222. doi: 10.1093/annonc/mdm285 PubMedCrossRefGoogle Scholar
  32. 32.
    Chau I, Legge S, Fumoleau P (2004) The vital role of education and information in patients receiving capecitabine (Xeloda). Eur J Oncol Nurs 8(Suppl 1):S41–S53. doi: 10.1016/j.ejon.2004.06.008 PubMedCrossRefGoogle Scholar
  33. 33.
    Faithfull S, Deery P (2004) Implementation of capecitabine (Xeloda) into a cancer centre: UK experience. Eur J Oncol Nurs 8(Suppl 1):S54–S62. doi: 10.1016/j.ejon.2004.06.009 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hesham Tawfik
    • 1
  • Yousri Rostom
    • 2
  • Hesham Elghazaly
    • 3
  1. 1.Clinical Oncology DepartmentTanta UniversityTantaEgypt
  2. 2.Clinical Oncology DepartmentAlexandria UniversityAlexandriaEgypt
  3. 3.Clinical Oncology DepartmentAin Shams UniversityCairoEgypt

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