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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

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Abstract

Purpose

Effective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and effective in first-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes.

Patients and methods

Forty patients (median age 52 years) with MBC received the combination of oral VRL 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, international, multicentre, phase II study. Cycles were repeated every 3 weeks. The primary endpoint was response rate (RR) evaluated by an independent panel review. Secondary objectives included safety, duration of response, progression-free survival, overall survival and quality of life.

Results

All the patients had received prior chemotherapy with anthracyclines and taxanes, 75% were refractory/resistant to anthracycline and/or taxane, 72.5% presented with visceral involvement and the last prior chemotherapy for 87.5% of the patients was for advanced disease setting. The median number of administered cycles per patient was 4 (range 1–31). Eight responses were documented and validated by an independent panel review, yielding RRs of 20% [95% CI: 9–35.6] in the intent-to-treat (treated) population and 23.5% [95% CI: 10.7–41.2] in the 34 evaluable patients. Median progression-free survival and median overall survival were 3.4 months [95% CI: 2.3–5.5] and 11.3 months [95% CI: 8.1–16.4], respectively. The principal toxicities were anaemia, neutropenia (rarely complicated; only one patient experienced febrile neutropenia), fatigue and gastrointestinal toxicities with very few grade 3–4 non-haematological toxicities.

Conclusions

In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an efficacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients’ population. Moreover, this well-tolerated combination offers the advantages of an all oral regimen.

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References

  1. Althuis MD, Dozier JD, Anderson WF et al (2005) Global trends in breast cancer incidence and mortality 1973–1997. Int J Epidemiol 34:405–412

    Article  PubMed  Google Scholar 

  2. Kamangar F, Dores GM, Anderson WF et al (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 24:2137–2150

    Article  PubMed  Google Scholar 

  3. Valero V, Hortobagyi GN (2003) Are anthracycline-taxane regimens the new standard of care in the treatment of metastatic breast cancer? J Clin Oncol 21:959–962

    Article  PubMed  Google Scholar 

  4. Longley DB, Johnston PG (2005) Molecular mechanism of drug resistance. J Pathol 205:275–292

    Article  CAS  PubMed  Google Scholar 

  5. Bernard-Marty C, Cardoso F, Piccart MJ (2004) Facts and controversies in systemic treatment of metastatic breast cancer. Oncologist 9:617–632

    Article  PubMed  Google Scholar 

  6. Binet S, Fellous A, Lataste H et al (1989) In situ analysis of the action of Navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16:5–8

    CAS  PubMed  Google Scholar 

  7. 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(1):35–40

    CAS  PubMed  Google Scholar 

  8. 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 Suppl 2(3):137 (abstract 279)

    Article  Google Scholar 

  9. Gridelli C, Parlier Y, Brandely M et al (2003) Oral chemotherapy and upper gastro-intestinal tolerance improvement of nausea and vomiting in non-small cell lung cancer patients treated with oral navelbine and standard antiemetic prophylaxis. Eur J Cancer Suppl 1(5):S240–S241 (abstract 801)

    Article  Google Scholar 

  10. Liu G, Franssen E, Fitch MI et al (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15:110–115

    CAS  PubMed  Google Scholar 

  11. Marty M, Fumoleau P, Adenis A et al (2001) Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol 12:1643–1649

    Article  CAS  PubMed  Google Scholar 

  12. Saif MW, Katirzoglou NA, Syrigos KN (2008) Capecitabine: an overview of the side effects and their management. Anticancer Drugs 19:447–464

    CAS  PubMed  Google Scholar 

  13. Fumoleau P, Largillier R, Clippe C et al (2004) Multicenter phase II study evaluating capecitabine monotherapy in patients with anthracyclines and taxane pretreated metastatic breast cancer. Eur J Cancer 40:536–542

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Sawada N, Fujimoto-Ouchi F, Ishikawa T et al (2002) Antitumor activity of combination therapy with capecitabine plus vinorelbine, and capecitabine plus gemcitabine in human tumor xenograft models. Proc Am Assoc Cancer Res 43:1088 (abstract 5388)

    Google Scholar 

  16. Lorusso V, Spada M, Giampaglia M et al (2006) Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (MBC). A phase II study of the GOIM (Gruppo Oncologico d’ell’Italia Meridionale). Ann Oncol 17(Suppl 7):15–17

    Google Scholar 

  17. Ahn JH, Kim SB, Kim TW, Ahn SH et al (2004) Capecitabine and vinorelbine in patients with metastatic breast cancer previously treated with anthracyclines and taxane. J Korean Med Sci 19:547–553

    Article  CAS  PubMed  Google Scholar 

  18. Davis AJ, Brew S, Gebski VJ et al (2007) Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer. Asia Pac J Clin Oncol 3:1–7

    Article  Google Scholar 

  19. Welt A, Von Minckwitz G, Oberhoff C et al (2005) Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Ann Oncol 16:64–69

    Article  CAS  PubMed  Google Scholar 

  20. Hess D, Thurlimann B, Pagani O et al (2004) Capecitabine and vinorelbine in elderly patients (≥65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99). Ann Oncol 15:1760–1765

    Article  CAS  PubMed  Google Scholar 

  21. Stuart N, Bishop L, Johnson SRD et al (2003) Vinorelbine and capecitabine for advanced breast cancer. A phase II study showing good activity and potential for further development. Proc Am Soc Clin Oncol (Abstr 183)

  22. Ghosn M, Kattan J, Farhat F et al (2006) Phase II trial of capecitabine and vinorelbine as first-line chemotherapy for metastatic breast cancer patients. Anticancer Res 26:2451–2456

    CAS  PubMed  Google Scholar 

  23. Nolè F, Catania G, Senna G et al (2006) Dose finding and pharmacokinetic study of an all-oral combination of oral vinorelbine and capecitabine for patients with metastatic breast cancer. Ann Oncol 17:322–329

    Article  PubMed  Google Scholar 

  24. Nolè F, Crivellari D, Mattioli R et al (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

    Article  PubMed  CAS  Google Scholar 

  25. Finek J, Holubec L Jr, Svoboda T et al (2009) A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer. Anticancer Res 29(2):667–670

    CAS  PubMed  Google Scholar 

  26. Green S, Weiss G (1992) Southwest Oncology Group standard response criteria, endpoint definition and toxicity criteria. Invest New Drugs 10:239–253

    Article  CAS  PubMed  Google Scholar 

  27. Pizzo PA (1993) Management of fever in patients with cancer and treatment-induced neutropenia. New Eng J Med 328:1323–1332

    Google Scholar 

  28. Carrick S, Parker S, Thornton CE et al (2009) Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 18(2):CD003372

    Google Scholar 

  29. Wilcken N, Dear R (2008) Chemotherapy in metastatic breast cancer: a summary of all randomized trials reported 2000–2007. Eur J Cancer 44(15):2218–2225

    Article  CAS  PubMed  Google Scholar 

  30. Bunnell C, Vahdat L, Schwartzberg L et al (2008) PhaseI/II study of ixabepilone plus capecitabine in anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer. Clin Breast Cancer 8(3):234–241

    Article  CAS  PubMed  Google Scholar 

  31. Thomas ES, Gomez HL, Li RK et al (2007) Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 25:5210–5217

    Article  CAS  PubMed  Google Scholar 

  32. Dean-Colomb W, Esteva FJ (2008) Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. Semin Oncol 35(Suppl 2):S31–S38

    Article  CAS  PubMed  Google Scholar 

  33. Petit T, Benider A, Yocine A et al (2006) Phase II study of an oxaliplatin/vinorelbine combination in patients with anthracycline-and taxane-pre-treatedmetastatic breast cancer. Anticancer Drugs 17:337–343

    Article  CAS  PubMed  Google Scholar 

  34. Sanchez-Escribano Morcuende R, Ales-Martinez JE, Aramburo Gonzalez PM (2007) Low dose gemcitabine plus cisplatin in a weekly-based regimen as salvage therapy for relapse breast cancer after taxane- anthracycline-containing regimens. Clin Transl Oncol 9:459–464

    Article  CAS  PubMed  Google Scholar 

  35. Ray-Coquard I, Biron P, Bachelot T et al (1998) Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens. Cancer 82:134–140

    Article  CAS  PubMed  Google Scholar 

  36. Tubiana-Mathieu N, Bougnoux P, Becquart D et al (2009) All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II trial. British J Cancer 101:232–237

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Royal Free Hospital, Londres, NW3 2QG, UK

    Alison Jones

  2. Royal Marsden Hospital, Sutton, SM2 5PT, UK

    Mary O’Brien

  3. Klinikum der Universität München, 80337, München, Germany

    Harald Sommer

  4. Instytut im M. Sklodowskiej Curie, 44-100, Gliwice, Poland

    Elzbieta Nowara

  5. Universitätsklinikum Essen, 45147, Essen, Germany

    Anja Welt

  6. Instytut im M. Sklodowskiej Curie, 02-781, Warsaw, Poland

    Tadeusz Pienkowski

  7. Instytut im M. Sklodowskiej Curie, 31-115, Krakow, Poland

    Janusz Rolski

  8. Institut de Recherche Pierre Fabre, Boulogne, France

    My-Linh Pham & Kevin Perraud

  9. Centre Hospitalier Lyon Sud and EA 3738 Université Claude Bernard Lyon I, Lyon, France

    Véronique Trillet-Lenoir

Authors
  1. Alison Jones
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  2. Mary O’Brien
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  3. Harald Sommer
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  4. Elzbieta Nowara
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  5. Anja Welt
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  7. Janusz Rolski
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  8. My-Linh Pham
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  9. Kevin Perraud
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  10. Véronique Trillet-Lenoir
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Corresponding author

Correspondence to Alison Jones.

Additional information

This study was supported by an unrestricted grant from Institut de Recherche Pierre Fabre, Boulogne, France.

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Jones, A., O’Brien, M., Sommer, H. et al. 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, 755–763 (2010). https://doi.org/10.1007/s00280-009-1081-y

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  • DOI: https://doi.org/10.1007/s00280-009-1081-y

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