Clinical Drug Investigation

, Volume 29, Issue 8, pp 551–555

Effects of Recombinant Human Granulocyte Colony-Stimulating Factor Filgrastim on ECG Parameters in Neutropenic Patients

A Single-Centre,Prospective Study
Short Communication


Background and objective: Human granulocyte colony-stimulating factor (G-CSF) is a haematopoietic hormone that promotes the growth, proliferation, differentiation and maturation of neutrophil precursors. Filgrastim is a recombinant human G-CSF. Myocardial infarction, atrial fibrillation and arrhythmia have been reported in several patients with malignancy receiving filgrastim, but a causal relationship with the drug has not been established. The purpose of this study was to investigate the changes in ECG parameters in neutropenic patients during treatment with filgrastim.

Methods: This was a single-centre, prospective study carried out in a hospital emergency room. Patients with neutropenia and malignancy who were required to receive filgrastim were eligible for the study. After a reference ECG had been obtained, filgrastim was administered to all patients at a dose of 5 µg/kg/day subcutaneously for 2 days. Follow-up ECGs were then obtained at 12-hourly intervals. Continuous telemetric monitoring was conducted throughout hospitalization.

Results: Serial ECG parameters were compared in 102 patients. There were no statistically significant differences between baseline and follow-up ECG measurements of rhythm, P-wave duration, PR interval, QRS-wave duration, corrected QT (QTc) interval, ECG axis, premature supraventricular events, ventricular arrhythmia, R-wave progression, right bundle branch block or left bundle branch block. There was a significant reduction in mean heart rate in subsequent ECGs compared with baseline (p≪0.05).

Conclusion: This study did not demonstrate any ECG changes other than a significant reduction in mean heart rate in this selected population of neutropenic patients given 2 days’ treatment with subcutaneous 5 µg/kg/day of filgrastim.


  1. 1.
    Borleffs JC, Bosschaert M, Vrehen HM, et al. Effect of escalating doses of recombinant human granulocyte colony-stimulating factor (filgrastim) on circulating neutrophils in healthy subjects. Clin Ther 1998; 20(4): 722–36PubMedCrossRefGoogle Scholar
  2. 2.
    Filgrastim. AHFS drug information [online]. Available from URL: a392033.htm [Accessed 2008 May 29]Google Scholar
  3. 3.
    Takahama H, Minamino T, Hirata A, et al. Granulocyte colony-stimulating factor mediates cardioprotection against ischemia/reperfusion injury via phosphatidylinositol-3-kinase/Akt pathway in canine hearts. Cardiovasc Drugs Ther 2006; 20(3): 159–65PubMedCrossRefGoogle Scholar
  4. 4.
    Lee JJ, Chung IJ, Ahn YK, et al. Life-threatening paroxysmal supraventricular tachycardia developed during granulocyte transfusion therapy for neutropenia-related infection. Leukemia 2000; 14(7): 1324–5PubMedCrossRefGoogle Scholar
  5. 5.
    Trillet-Lenoir V, Manegold JGC, Von Pawel J, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A: 319–24PubMedCrossRefGoogle Scholar
  6. 6.
    Holmes FA, Jones SE, Shaughnessy JO. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 2002; 13: 903–9PubMedCrossRefGoogle Scholar
  7. 7.
    Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte-colony stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell-lung cancer. N Engl J Med 1991; 325: 164–70PubMedCrossRefGoogle Scholar
  8. 8.
    Lindemann A, Rumberger B. Vascular complications in patients treated with granulocyte colony-stimulating factor (G-CSF). Eur J Cancer 1993; 29A(16): 2338–9PubMedCrossRefGoogle Scholar
  9. 9.
    Kuroiwa M, Okamura T, Kanaji T, et al. Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers. Int J Hematol 1996; 63(4): 311–6PubMedCrossRefGoogle Scholar
  10. 10.
    Conti JA, Scher HI. Acute arterial thrombosis after escalated-dose methotrexate, vinblastin, doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor: a possible new recombinant granulocyte colony-stimulating factor toxicity. Cancer 1992; 70(11): 2699–702PubMedCrossRefGoogle Scholar
  11. 11.
    Kaptan K, Beyan C, Ifran A. Granulocyte colony-stimulating factor. CMAJ 2006; 175(9): 1095PubMedGoogle Scholar
  12. 12.
    Amgen. Neupogen® (filgrastim) [prescribing information]. Thousand Oaks (CA): Amgen, 2004 Dec 20Google Scholar
  13. 13.
    Raisch DW, Holdsworth MT, Winter SS, et al. Economic comparison of home-care-based versus hospital-based treatment of chemotherapy-induced febrile neutropenia in children. Value Health 2003; 6(2): 158–66PubMedCrossRefGoogle Scholar
  14. 14.
    Spencer A, Reed K, Arthur C. Pilot study of an outpatient-based approach for advanced lymphoma using vinorelbine, gemcitabine and filgrastim. Intern Med J 2007; 37(11): 760–6PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  • Ozlem Guneyse
    • 1
  • Ozge Ecmel Onur
    • 1
  • Arzu Denizbasi
    • 1
  1. 1.Department of Emergency MedicineMarmara University School of MedicineIstanbulTurkey

Personalised recommendations