Cancer Chemotherapy and Pharmacology

, Volume 57, Issue 5, pp 554–558 | Cite as

Oral vinorelbine alone or in combination with trastuzumab in advanced breast cancer: results from a pilot trial

  • Rupert Bartsch
  • Catharina Wenzel
  • Ursula Pluschnig
  • Dagmar Hussian
  • Ursula Sevelda
  • Gottfried J. Locker
  • Robert Mader
  • Christoph C. Zielinski
  • Guenther G. StegerEmail author
Original Article


Introduction: We evaluated the efficacy of oral vinorelbine (OV) (Navelbine oral® Boeringer-Ingelheim Austria) in patients with advanced breast cancer as first-line therapy or after progressing under earlier line chemotherapies alone or in combination with trastuzumab (T). Patients and methods: Seventy-eight patients [median age: 63.5 years (y), range (r): 38–84 years] were included into this trial. Patients with her-2/neu positive tumours received a combination of OV and T. Treatment effect was evaluated every three cycles and treatment continued until progression. OV was administered in a dose of 60 mg/m2 on day 1 and 8, q = 21 days, and no dose escalation to 80 mg/m2 was performed. Results: We observed a complete response in 5.9% of patients, partial remission in 22.1%, stable disease (SD) > 6 months in 33.8%, SD < 6 months in 2.9%, and progression despite treatment in 35.3%, respectively. Time to progression was 6 months (range 1–23+). The main toxicities consisted of nausea/vomiting (N/V) and neutropenia. Grade IV neutropenia was found in 5 patients (6.4%), grade III in 6 patients (7.7%) and grade I and II in 11.5%. We did not find any grade IV N/V in our patients, however, grade III N/V was observed in 3.8%. No other grade III and IV toxicities were reported. Conclusion: OV appears to be effective in the treatment of advanced breast cancer at the dose and schedule chosen. It is well tolerated, effective, and the oral formulation is an advantage for the patients as well as for the nursing staff.


Advanced breast cancer Oral vinorelbine Palliative chemotherapy Trastuzumab Immunotherapy 


  1. 1.
    Ligibel JA, Winer EP (2002) Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol 29:38–43PubMedGoogle Scholar
  2. 2.
    Thomssen C (2001) Trials of new combinations of Herceptin in metastatic breast cancer. Anticancer Drugs 12(Suppl. 4):S19–S25PubMedGoogle Scholar
  3. 3.
    Vogel CL, Franco SX (2003) Clinical experience with trastuzumab (herceptin). Breast J 9:452–462CrossRefPubMedGoogle Scholar
  4. 4.
    Burstein HJ, Harris LN, Marcom PK, et al (2003) 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 21:2889–2895CrossRefPubMedGoogle Scholar
  5. 5.
    Winer EP, Burstein HJ (2001) New combinations with herceptin in metastatic breast cancer. Oncology 61(Suppl. 2):50–57PubMedCrossRefGoogle Scholar
  6. 6.
    Jahanzeb M, Mortimer JE, Yunus F, et al (2002) Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with Her2(+) metastatic breast cancer. Oncologist 7:410–417CrossRefPubMedGoogle Scholar
  7. 7.
    Montemurro F, Valabrega G, Aglietta M (2004) Trastuzumab-based combination therapy for breast-cancer. Expert Opin Pharmacother 5:81–96CrossRefPubMedGoogle Scholar
  8. 8.
    Jahanzeb M (2003) Trastuzumab-based combinations in metastatic breast cancer: how to make a choice. Clin Breast Cancer 1:28–38CrossRefGoogle Scholar
  9. 9.
    Suzuki Y, Tokuda Y, Saito Y, et al (2003) Combination of trastuzumab and vinorelbine in metastatic breast cancer. Jpn J Clin Oncol 33:514–517CrossRefPubMedGoogle Scholar
  10. 10.
    Winer EP, Burstein HJ (2001) New combinations with herceptin in metastatic breast cancer. Oncology 61(Suppl. 2):50–57PubMedCrossRefGoogle Scholar
  11. 11.
    Burstein HJ, Kuter I, Campos SM, et al (2004) Clinical activity of trastuzumab and vinorelbine in women with Her2-overexpressing breast cancer. J Clin Oncol 15:2722–2730Google Scholar
  12. 12.
    Leveque D, Jehl F (1996) Clinical pharmacokinetics of vinorelbine. Clin Pharmacokinet 32:323Google Scholar
  13. 13.
    Smith GA (1995) Current status of vinorelbine for breast cancer. Oncology (Huntingt) 9:767–773Google Scholar
  14. 14.
    Rossi A, Gridelli C, Gebbia V, et al (2003) Single agent vinorelbine as first-line chemotherapy in elderly patients with advanced breast cancer. Anticancer Res 23:1657–1664PubMedGoogle Scholar
  15. 15.
    Depierre A, Freyer G, Jassem J, et al (2001) Oral vinorelbine: feasibility and safety profile. Ann Oncol 12:1677–1681CrossRefPubMedGoogle Scholar
  16. 16.
    Variol P, Nguyen L, Tranchand B, et al (2002) A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine. Eur J Clin Pharmacol 58:467–476CrossRefPubMedGoogle Scholar
  17. 17.
    Burstein HJ, Kuter I, Campos SM, et al (2004) Clinical activity of trastuzumab and vinorelbine in women with Her2-overexpressing metastatic breast cancer. J Clin Oncol 19:2722–2730Google Scholar
  18. 18.
    Bonneterre J, Chevalier B, Focan C, et al (2001) Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in patients with advanced breast cancer (ABC). Ann Oncol 12:1683–1691CrossRefPubMedGoogle Scholar
  19. 19.
    Carlson RW (1998) Quality of life issues in the treatment of metastatic breast cancer. Oncology (Huntingt) 12:27–31Google Scholar
  20. 20.
    Leyland-Jones B, Gelmon K, Ayoub JP, et al (2003) Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 21:3965–3971CrossRefPubMedGoogle Scholar
  21. 21.
    Kaplan EL, Meier P (1958) Non parametric estimation for incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  22. 22.
    O´Shaughnessy J, Miles D, Vukelja S (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823CrossRefPubMedGoogle Scholar
  23. 23.
    Freyer G, Delozier T, Lichinister M, et al (2003) Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 21:35–40PubMedGoogle Scholar
  24. 24.
    Trillet-Lenoir V, Sommer H, Delozier T, et al (2004) Oral vinorelbine in metastatic breast cancer: long term results of 2 phase II studies. Eur J Cancer 2(Suppl.):Abstract 279Google Scholar
  25. 25.
    Slamon DJ, Clark GM, Wong SG, et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235:177–182PubMedCrossRefGoogle Scholar
  26. 26.
    Boss JS, Fletcher JA, Linette GP (2003) The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 8:307–325CrossRefPubMedGoogle Scholar
  27. 27.
    Paik S, Hazan R, Fisher ER, et al (1990) Pathologic finding from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein expression in primary breast cancer. J Clin Oncol 8:103–112PubMedGoogle Scholar
  28. 28.
    Kallioniemi OP, Holli K, Visakorpi T, et al (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 4:650–655CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Rupert Bartsch
    • 1
  • Catharina Wenzel
    • 1
  • Ursula Pluschnig
    • 1
  • Dagmar Hussian
    • 1
  • Ursula Sevelda
    • 1
  • Gottfried J. Locker
    • 1
  • Robert Mader
    • 1
  • Christoph C. Zielinski
    • 1
    • 2
    • 3
  • Guenther G. Steger
    • 1
    Email author
  1. 1.Department of Internal Medicine I, Division of OncologyMedical University of ViennaViennaAustria
  2. 2.Chair of Medical OncologyMedical University of ViennaViennaAustria
  3. 3.Ludwig Boltzmann Institute for Clinical OncologyMedical University of ViennaViennaAustria

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