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Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 5, pp 1315–1322 | Cite as

Gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer

  • Ningning DongEmail author
  • Mingyu Wang
  • Huiqing Li
  • Yongchun Cui
  • Qisen Guo
Original Article

Abstract

Purpose

To evaluate the efficacy and safety of gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC).

Patients and methods

Elderly patients with MBC received gemcitabine 1,000 mg m−2 and vinorelbine 25 mg m−2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles. The primary end points were objective response and toxicity. The secondary end points included progression-free survival (PFS), overall survival (OS), and prognostic factors associated with disease control, PFS, and OS.

Results

Fifty-one patients with a median age of 73 years (range, 65–84 years) were included. The response rate according to Response Evaluation Criteria in Solid Tumors was 33.3% (95% confidence interval [CI], 20.4 to 46.2%). At a median follow-up of 16.2 months, median PFS and OS were 6.2 (95% CI, 4.6 to 7.8) and 17.0 months (95% CI, 14.5 to 19.5), respectively. Grade 3 to 4 adverse events included neutropenia (25.5%), anemia (13.7%), thrombocytopenia (9.8%), fatigue (5.9%), constipation (3.9%), neuropathy (3.9%), and hepatotoxicity (3.9%). Neutropenic fever occurred in 2 patients. There was one toxic death due to massive gastrointestinal hemorrhage. The study of prognostic factors did not reveal any predictive factor of disease control, while response to treatment and Eastern Cooperative Oncology Group performance status was the main factor conditioning PFS and OS, respectively.

Conclusion

Gemcitabine in combination with vinorelbine is active and safe in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer.

Keywords

Gemcitabine Vinorelbine Chemotherapy Elder Metastatic breast cancer 

Notes

Acknowledgment

We thank Dr. Jun Ren for his assistance during the writing of the article.

Conflict of interest

All authors indicated no potential conflicts of interest.

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRefGoogle Scholar
  2. 2.
    Cyr A, Gillanders WE, Aft RL, Eberlein TJ, Margenthaler JA (2011) Breast cancer in elderly women (≥80 years): variation in standard of care? J Surg Oncol 103:201–206PubMedCrossRefGoogle Scholar
  3. 3.
    Carlson RW, Moench S, Hurria A, Balducci L, Burstein HJ, Goldstein LJ, Gradishar WJ, Hughes KS, Jahanzeb M, Lichtman SM, Marks LB, McClure JS, McCormick B, Nabell LM, Pierce LJ, Smith ML, Topham NS, Traina TA, Ward JH, Winer EP (2008) NCCN task force report: breast cancer in the older woman. J Natl Compr Cancer Netw 6(Suppl 4):S1–S25Google Scholar
  4. 4.
    Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061–2067PubMedCrossRefGoogle Scholar
  5. 5.
    Crivellari D, Aapro M, Leonard R, von Minckwitz G, Brain E, Goldhirsch A, Veronesi A, Muss H (2007) Breast cancer in the elderly. J Clin Oncol 25:1882–1890PubMedCrossRefGoogle Scholar
  6. 6.
    Oostendorp LJ, Stalmeier PF, Donders AR, van der Graaf WT, Ottevanger PB (2011) Efficacy and safety of palliative chemotherapy for patients with advanced breast cancer pretreated with anthracyclines and taxanes: a systematic review. Lancet Oncol 12:1053–1061PubMedCrossRefGoogle Scholar
  7. 7.
    Modi S, Currie VE, Seidman AD, Bach AM, Panageas KS, Theodoulou M, Moasser MM, D’Andrea GM, Lake DE, Choi J, Norton L, Hudis CA (2005) A phase II trial of gemcitabine in patients with metastatic breast cancer previously treated with an anthracycline and taxane. Clin Breast Cancer 6:55–60PubMedCrossRefGoogle Scholar
  8. 8.
    Rha SY, Moon YH, Jeung HC, Kim YT, Sohn JH, Yang WI, Suh CO, Kim GE, Roh JK, Chung HC (2005) Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer. Breast Cancer Res Treat 90:215–221PubMedCrossRefGoogle Scholar
  9. 9.
    Smorenburg CH, Bontenbal M, Seynaeve C, van Zuylen C, de Heus G, Verweij J, de Wit R (2001) Phase II study of weekly gemcitabine in patients with metastatic breast cancer relapsing or failing both an anthracycline and a taxane. Breast Cancer Res Treat 66:83–87PubMedCrossRefGoogle Scholar
  10. 10.
    Seo HY, Lee HJ, Woo OH, Park KH, Woo SU, Yang DS, Kim AR, Lee JB, Lee ES, Kim YH, Kim JS, Seo JH (2011) Phase II study of vinorelbine monotherapy in anthracycline and taxane pre-treated metastatic breast cancer. Invest New Drugs 29:360–365PubMedCrossRefGoogle Scholar
  11. 11.
    Toi M, Saeki T, Aogi K, Sano M, Hatake K, Asaga T, Tokuda Y, Mitsuyama S, Kimura M, Kobayashi T, Tamura M, Tabei T, Shin E, Nishimura R, Ohno S, Takashima S (2005) Late phase II clinical study of vinorelbine monotherapy in advanced or recurrent breast cancer previously treated with anthracyclines and taxanes. Jpn J Clin Oncol 35:310–315PubMedCrossRefGoogle Scholar
  12. 12.
    Jara-Sánchez C, Martín M, García-Sáenz JA, Barnada A, Fernández-Aramburo A, López-Vega JM, Pelegrí A, Alba E, Casado A, Spanish Group for Research in Breast Cancer (2003) Vinorelbine as a 96-hour continuous infusion in heavily pretreated patients with metastatic breast cancer: a cooperative study by the GEICAM group. Clin Breast Cancer 3:399–404PubMedCrossRefGoogle Scholar
  13. 13.
    Zelek L, Barthier S, Riofrio M, Fizazi K, Rixe O, Delord JP, Le Cesne A, Spielmann M (2001) Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer 92:2267–2272PubMedCrossRefGoogle Scholar
  14. 14.
    Udom DI, Vigushin DM, Linardou H, Graham H, Palmieri C, Coombes RC (2000) Two weekly vinorelbine: administration in patients who have received at least two prior chemotherapy regimens for advanced breast cancer. Eur J Cancer 36:177–182PubMedCrossRefGoogle Scholar
  15. 15.
    Livingston RB, Ellis GK, Gralow JR, Williams MA, White R, McGuirt C, Adamkiewicz BB, Long CA (1997) Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor support in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 15:1395–1400PubMedGoogle Scholar
  16. 16.
    Kim HJ, Kim JS, Seo MD, Oh SY, Oh DY, Kim JH, Lee SH, Kim DW, Im SA, Kim TY, Heo DS, Bang YJ (2008) Gemcitabine and vinorelbine combination chemotherapy in anthracycline- and taxane-pretreated advanced breast cancer. Cancer Res Treat 40:81–86PubMedCrossRefGoogle Scholar
  17. 17.
    Gennatas C, Michalaki V, Mouratidou D, Tsavaris N, Andreadis C, Psychogios J, Poulakaki N (2006) Gemcitabine in combination with vinorelbine for heavily pretreated advanced breast cancer. Anticancer Res 26:549–552PubMedGoogle Scholar
  18. 18.
    Park IH, Ro J, Lee KS, Kim SN, Yun YH, Nam BH (2010) Phase II study of gemcitabine in combination with vinorelbine versus gemcitabine followed by vinorelbine for metastatic breast cancer. Invest New Drugs 28:659–669PubMedCrossRefGoogle Scholar
  19. 19.
    Donadio M, Ardine M, Berruti A, Ritorto G, Fea F, Mistrangelo M, Coccorullo Z, Bergnolo P, Comandone A, Bertetto O (2003) Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer: a phase II study. Cancer Chemother Pharmacol 52:147–152PubMedCrossRefGoogle Scholar
  20. 20.
    Martín M, Ruiz A, Muñoz M, Balil A, García-Mata J, Calvo L, Carrasco E, Mahillo E, Casado A, García-Saenz JA, Escudero MJ, Guillem V, Jara C, Ribelles N, Salas F, Soto C, Morales-Vasquez F, Rodríguez CA, Adrover E, Mel JR (2007) Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol 8:219–225PubMedCrossRefGoogle Scholar
  21. 21.
    Nicolaides C, Dimopoulos MA, Samantas E, Bafaloukos D, Kalofonos C, Fountzilas G, Razi E, Kosmidis P, Pavlidis N (2000) Gemcitabine and vinorelbine as second line treatment in patients with metastatic breast cancer progressing after first line taxane-based chemotherapy: A phase II study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 11:873–875PubMedCrossRefGoogle Scholar
  22. 22.
    Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkiewicz B, White R, McGuirt C (1999) Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Ann Oncol 10:397–402PubMedCrossRefGoogle Scholar
  23. 23.
    Basso U, Monfardini S (2004) Multidimensional geriatric evaluation in elderly cancer patients: a practical approach. Eur J Cancer Care (Engl) 13:424–433CrossRefGoogle Scholar
  24. 24.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  25. 25.
    Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181PubMedCrossRefGoogle Scholar
  26. 26.
    Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10PubMedCrossRefGoogle Scholar
  27. 27.
    Pallis AG, Boukovinas I, Ardavanis A, Varthalitis I, Malamos N, Georgoulias V, Mavroudis D (2011) A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol (Epub ahead of print)Google Scholar
  28. 28.
    Debled M, Madranges N, Mertens C, Durand M, Brouste V, Brain E, Mauriac L (2011) First-line chemotherapy for metastatic breast cancer in patients ≥75 years: a retrospective single-centre analysis. Crit Rev Oncol Hematol 80:171–179PubMedCrossRefGoogle Scholar
  29. 29.
    Blum JL, Kohles J, McKenna E, Scotto N, Hu S, Odom D, Kaye JA, Glück S (2011) Association of age and overall survival in capecitabine-treated patients with metastatic breast cancer in clinical trials. Breast Cancer Res Treat 125:431–439PubMedCrossRefGoogle Scholar
  30. 30.
    Pierga JY, Fumoleau P, Brewer Y, Zelek L, Martin D, Turpin FL, Goudier MJ, Gil-Delgado M, Baticle JL, Namer M, Chollet P, Sutherland W, Barats JC, Cooperative Group of the French capecitabine compassionate use program (2004) Efficacy and safety of single agent capecitabine in pretreated metastatic breast cancer patients from the French compassionate use program. Breast Cancer Res Treat 88:117–129PubMedCrossRefGoogle Scholar
  31. 31.
    Rabinovich M, Vallejo C, Bianco A, Perez J, Machiavelli M, Leone B, Romero A, Rodriguez R, Cuevas M, Dansky C (1992) Development and validation of prognostic models in metastatic breast cancer: a GOCS study. Oncology 49:188–195PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ningning Dong
    • 1
    Email author
  • Mingyu Wang
    • 2
  • Huiqing Li
    • 3
  • Yongchun Cui
    • 4
  • Qisen Guo
    • 2
  1. 1.Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Medical Oncology DepartmentPeking University School of Oncology, Beijing Cancer Hospital & InstituteBeijingChina
  2. 2.Chemotherapy DepartmentShandong Tumor Hospital and InstituteJinanChina
  3. 3.Epidemiology Department, Institute of Basic MedicineShandong Academy of Medical SciencesJinanChina
  4. 4.Clinical Trial CenterShandong Tumor Hospital and InstituteJinanChina

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