International Journal of Clinical Pharmacy

, Volume 35, Issue 1, pp 45–50 | Cite as

Predictors of response of patients with solid tumors to granulocyte colony-stimulating factor

  • Hiroaki OhnakaEmail author
  • Hitoshi Tsukamoto
  • Toshiaki Nakamura
  • Ryoichi Yano
  • Kyohei Watanabe
  • Toshiaki Igarashi
  • Nobuyuki Goto
  • Mikio Masada
Research Article


Background Granulocyte colony-stimulating factor administration is an important component of supportive therapy in chemotherapy-induced leukopenia. Although patient response to granulocyte colony-stimulating factor administration is known to vary, the factors responsible for poor response have not been identified. Objective To identify the predictors of the responses of patients with solid tumors to granulocyte colony-stimulating factor. Setting A 600-bed university hospital offering secondary and tertiary care in Japan. Methods This retrospective cohort study examined the response of 181 patients with solid tumors who were administered prophylactic granulocyte colony-stimulating factor for the first time after they developed severe grade 3/4 leukopenia (white blood cell count <2,000 × 10−9/L) because of adjuvant or neoadjuvant chemotherapy. The granulocyte colony-stimulating factor response was defined as the length of the leukocyte recovery period, which was assessed as the period within which the normal white blood cell count (white blood cell count >3,000 × 10−9/L) is reached after the first dosage of granulocyte colony-stimulating factor. After classification of the patients as either poor or normal granulocyte colony-stimulating factor responders according to the confidence interval of the recovery period, their characteristics were compared. Main outcome measure The time for recovery to normal white blood cell count was 2–7 days (90 % confidence interval), and the cutoff value for differentiating poor responders (n = 14) from normal responders (n = 167) was 8 days. Univariate analysis identified previous radiotherapy, number of chemotherapy courses, high granulocyte colony-stimulating factor dosage, and hypoalbuminemia to be significantly associated with granulocyte colony-stimulating factor response. Multivariate analysis identified undergoing four or more chemotherapy courses (odds ratio = 5.09; 95 % confidence interval, 1.14–22.71) and heart failure (odds ratio = 5.96; 95 % confidence interval, 1.09–32.57) to be significantly associated with poor granulocyte colony-stimulating factor response. Conclusions Undergoing four or more chemotherapy courses and heart failure are independent risk factors for poor response to granulocyte colony-stimulating factor. These findings may help prevent the complications of leukopenia during chemotherapy and highlight the need to develop better strategies for preventing and treating infectious disease in patients undergoing granulocyte colony-stimulating factor administration.


Chemotherapy Granulocyte colony-stimulating factor Heart failure Leukopenia Neutropenia 





This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflicts of interest



  1. 1.
    Lalami Y, Paesmans M, Muanza F, Barette M, Plehiers B, Dubreucq L, et al. Can we predict the duration of chemotherapy-induced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis. Ann Oncol. 2006;17:507–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–205.PubMedCrossRefGoogle Scholar
  3. 3.
    Lyman GH. Guidelines of the national comprehensive cancer network on the use of myeloid growth factors with cancer chemotherapy: a review of evidence. J Natl Compr Cancer Netw. 2005;3:557–71.Google Scholar
  4. 4.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Kuderer NM, Dale DC, Crawford J, Lyman GH. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. 2007;25:3158–67.PubMedCrossRefGoogle Scholar
  6. 6.
    Klastersky J, Awada A, Aoun M, Paesmans M. Should the indications for the use of myeloid growth factors for the prevention of febrile neutropenia in cancer patients be extended? Curr Opin Oncol. 2009;21:297–302.PubMedCrossRefGoogle Scholar
  7. 7.
    Fukuoka M, Masuda N, Negoro S, Matsui K, Yana T, Kudoh S, et al. CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer. Br J Cancer. 1997;75:306–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Ahn S, Lee YS, Chun YH, Kwon IH, Kim W, Lim KS, et al. Predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia. Support Care Cancer. 2011;19:1151–8.PubMedCrossRefGoogle Scholar
  9. 9.
    National Cancer Institute. Common terminology criteria for adverse events v3.0. Available via of subordinate document. Accessed Oct 2009.
  10. 10.
    Tu JV, Austin PC, Walld R, Roos L, Agras J, McDonald KM. Development and validation of the Ontario acute myocardial infarction mortality prediction rules. J Am Coll Cardiol. 2001;37:992–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Austin PC, Austin PC. Bootstrap methods for developing predictive models. Am Stat. 2004;58:131–7.CrossRefGoogle Scholar
  12. 12.
    Chang J, Geary CG, Testa NG. Long-term bone marrow damage after chemotherapy for acute myeloid leukaemia does not improve with time. Br J Haematol. 1990;75:68–72.PubMedCrossRefGoogle Scholar
  13. 13.
    Mauch P, Constine L, Greenberger J, Knospe W, Sullivan J, Liesveld JL, et al. Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys. 1995;31:1319–39.PubMedCrossRefGoogle Scholar
  14. 14.
    Kell R, Haunstetter A, Dengler TJ, Zugck C, Kübler W, Haass M. Do cytokines enable risk stratification to be improved in NYHA functional class III patients? Comparison with other potential predictors of prognosis. Eur Heart J. 2002;23:70–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Parissis JT, Adamopoulos SN, Venetsanou KF, Karas SM, Kremastinos DT. Elevated plasma amylase levels in advanced chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy: correlation with circulating interleukin-6 activity. J Interferon Cytokine Res. 2003;23:329–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Parissis JT, Adamopoulos S, Venetsanou KF, Mentzikof DG, Karas SM, Kremastinos DT. Clinical and neurohormonal correlates of circulating granulocyte-macrophage colony-stimulating factor in severe heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2000;86:707–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Jug B, Salobir BG, Vene N, Sebestjen M, Sabovic M, Keber I. Interleukin-6 is a stronger prognostic predictor than high-sensitive C-reactive protein in patients with chronic stable heart failure. Heart Vessels. 2009;24:271–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Nicola NA, Vadas MA, Lopez AF. Down-modulation of receptors for granulocyte colony-stimulating factor on human neutrophils by granulocyte-activating agents. J Cell Physiol. 1986;128:501–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Khwaja A, Carver J, Jones HM, Paterson D, Linch DC. Expression and dynamic modulation of the human granulocyte colony-stimulating factor receptor in immature and differentiated myeloid cells. Br J Haematol. 1993;85:254–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Hiroaki Ohnaka
    • 1
    Email author
  • Hitoshi Tsukamoto
    • 1
  • Toshiaki Nakamura
    • 1
  • Ryoichi Yano
    • 1
  • Kyohei Watanabe
    • 1
  • Toshiaki Igarashi
    • 1
  • Nobuyuki Goto
    • 2
  • Mikio Masada
    • 1
  1. 1.Department of PharmacyUniversity of Fukui HospitalFukuiJapan
  2. 2.Department of Drug Informatics, Faculty of PharmacyMeijo UniversityNagoyaJapan

Personalised recommendations