Supportive Care in Cancer

, Volume 27, Issue 3, pp 1099–1108 | Cite as

Real-world use of granulocyte colony-stimulating factor in ambulatory breast cancer patients: a cross-sectional study

  • Florence Van Ryckeghem
  • Chloë Haverbeke
  • Wim Wynendaele
  • Guy Jerusalem
  • Luc Somers
  • Anke Van den broeck
  • Sofie Vingerhoedt
  • Simon Van BelleEmail author
Original Article



To prevent febrile neutropenia (FN), European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend primary prophylaxis with granulocyte colony-stimulating factors (PPG) for patients at high risk (≥ 20%) of FN. In Belgium, the use of PPG is restricted by specific reimbursement criteria. The impact of these criteria on PPG use and adherence to guidelines is unknown.


This multicentre, cross-sectional, observational study aimed to describe PPG use by FN risk category in breast cancer patients who were scheduled to receive myelosuppressive chemotherapy in outpatient clinics in Belgium during a 2-week period between 13 October and 12 December 2014.


In total, 490 patients were enrolled. Median age was 57.0 years. Based on their chemotherapy regimen, 53.9, 5.1 and 41.0% of patients were at a low, intermediate and high risk of FN, respectively. Overall, 39.8% of patients received PPG (17.0, 12.0 and 73.1% of those receiving low-, intermediate- and high-risk regimens, respectively). In the high-risk category, PPG was used in 89.9% of dose-dense and in 25.0% of classical chemotherapy regimens. PPG use was adherent to EORTC guidelines in 75.3% of patients (30.6% appropriate use, 44.7% appropriate non-use). EORTC guidelines would recommend PPG use in 46.1% of this study population (n = 226), and its use was reimbursable in Belgium in 76.1% of these patients (n = 172), but only 66.4% of them received PPG (n = 150).


Both Belgian reimbursement criteria and physician decision-making led to a proportion of patients for whom PPG treatment was recommended but finally not receiving it.


Breast cancer Chemotherapy Febrile neutropenia Granulocyte colony-stimulating factor Prophylaxis 



Authors had access to primary data, analyses and study reports. Qualified researchers may request data from Amgen clinical studies. Complete details are available at the following:

Funding information

Amgen Inc. ran and funded this study, all analyses and the medical writing support. Medical writing support, funded by Amgen Belgium, was provided by Kelly Soady PhD of Oxford PharmaGenesis, Oxford, UK.

Compliance with ethical standards

Florence Van Rijckegem, Chloë Haverbeke, Wim Wynendaele and Simon Van Belle have no conflicts of interest to disclose; Guy Jerusalem disclosed consulting fees from Amgen; Luc Somers is an external consultant to Amgen BeLux; Anke Van den broeck and Sofie Vingerhoedt are employees of Amgen BeLux.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

520_2018_4399_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 17 kb)


  1. 1.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C, European Organisation for Research Treatment of Cancer (2011) 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 47:8–32. CrossRefGoogle Scholar
  2. 2.
    Crawford J, Dale DC, Lyman GH (2004) Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer 100:228–237. CrossRefGoogle Scholar
  3. 3.
    Naeim A, Henk HJ, Becker L, Chia V, Badre S, Li X, Deeter R (2013) Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer 13:11. CrossRefGoogle Scholar
  4. 4.
    Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, Herrstedt J, Committee EG (2016) Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol 27:v111–v118. CrossRefGoogle Scholar
  5. 5.
    Wang L, Baser O, Kutikova L, Page JH, Barron R (2015) The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer 23:3131–3140. CrossRefGoogle Scholar
  6. 6.
    Assi H, Murray J, Boyle L, Rayson D (2014) Incidence of febrile neutropenia in early stage breast cancer patients receiving adjuvant FEC-D treatment. Support Care Cancer 22:3227–3234. CrossRefGoogle Scholar
  7. 7.
    Kosaka Y, Rai Y, Masuda N, Takano T, Saeki T, Nakamura S, Shimazaki R, Ito Y, Tokuda Y, Tamura K (2015) Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer 23:1137–1143. CrossRefGoogle Scholar
  8. 8.
    Madarnas Y, Dent SF, Husain SF, Robinson A, Alkhayyat S, Hopman WM, Verreault JL, Vandenberg T (2011) Real-world experience with adjuvant fec-d chemotherapy in four Ontario regional cancer centres. Curr Oncol 18:119–125Google Scholar
  9. 9.
    Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, Neumann TA, Schwartzberg LS (2005) First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 23:1178–1184. CrossRefGoogle Scholar
  10. 10.
    Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P, Siena S, Lalisang RI, Samonigg H, Clemens MR, Zani V, Liang BC, Renwick J, Piccart MJ (2003) A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 14:29–35CrossRefGoogle Scholar
  11. 11.
    Holmes FA, O'Shaughnessy JA, Vukelja S, Jones SE, Shogan J, Savin M, Glaspy J, Moore M, Meza L, Wiznitzer I, Neumann TA, Hill LR, Liang BC (2002) Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 20:727–731. CrossRefGoogle Scholar
  12. 12.
    Baden LR, Swaminathan S, Angarone M, Blouin G, Camins BC, Casper C, Cooper B, Dubberke ER, Engemann AM, Freifeld AG, Greene JN, Ito JI, Kaul DR, Lustberg ME, Montoya JG, Rolston K, Satyanarayana G, Segal B, Seo SK, Shoham S, Taplitz R, Topal J, Wilson JW, Hoffmann KG, Smith C (2016) Prevention and treatment of cancer-related infections, version 2.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 14:882–913CrossRefGoogle Scholar
  13. 13.
    Smith TJ, Bohlke K, Armitage JO (2015) Recommendations for the use of white blood cell growth factors: American Society of Clinical Oncology clinical practice guideline update. J Oncol Pract 11:511–513. CrossRefGoogle Scholar
  14. 14.
    Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM (2010) Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 102:1845–1854. CrossRefGoogle Scholar
  15. 15.
    Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, Barni S (2015) Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials. Breast Cancer Res Treat 151:251–259. CrossRefGoogle Scholar
  16. 16.
    Perez E, Muss HB (2005) Optimizing adjuvant chemotherapy in early-stage breast cancer. Oncology (Williston Park) 19:1759–1767 discussion 1768, 1772–1754, 1777–1758Google Scholar
  17. 17.
    Do T, Medhekar R, Bhat R, Chen H, Niravath P, Trivedi MV (2015) The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis. Breast Cancer Res Treat 153:591–597. CrossRefGoogle Scholar
  18. 18.
    Redana S, Sharp A, Lote H, Mohammed K, Papadimitraki E, Capelan M, Ring A (2016) Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: an off study population. Breast 30:13–18. CrossRefGoogle Scholar
  19. 19.
    Pittman NM, Hopman WM, Mates M (2015) Emergency room visits and hospital admission rates after curative chemotherapy for breast cancer. J Oncol Pract 11:120–125. CrossRefGoogle Scholar
  20. 20.
    Krzemieniecki K, Sevelda P, Erdkamp F, Smakal M, Schwenkglenks M, Puertas J, Trojan A, Szabo Z, Bendall K, Maenpaa J (2014) Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy—findings from clinical practice. Support Care Cancer 22:667–677. CrossRefGoogle Scholar
  21. 21.
    Freyer G, Kalinka-Warzocha E, Syrigos K, Marinca M, Tonini G, Ng SL, Wong ZW, Salar A, Steger G, Abdelsalam M, DeCosta L, Szabo Z (2015) Attitudes of physicians toward assessing risk and using granulocyte colony-stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia. Med Oncol 32:236. CrossRefGoogle Scholar
  22. 22.
    Gerlier L, Lamotte M, Awada A, Bosly A, Bries G, Cocquyt V, Focan C, Henry S, Lalami Y, Machiels JP, Mebis J, Straetmans N, Verhoeven D, Somers L (2010) The use of chemotherapy regimens carrying a moderate or high risk of febrile neutropenia and the corresponding management of febrile neutropenia: an expert survey in breast cancer and non-Hodgkin’s lymphoma. BMC Cancer 10:642. CrossRefGoogle Scholar
  23. 23.
    Choi MR, Solid CA, Chia VM, Blaes AH, Page JH, Barron R, Arneson TJ (2014) Granulocyte colony-stimulating factor (G-CSF) patterns of use in cancer patients receiving myelosuppressive chemotherapy. Support Care Cancer 22:1619–1628. CrossRefGoogle Scholar
  24. 24.
    Link H, Nietsch J, Kerkmann M, Ortner P, for the Suppportive Care Group (ASORS) of the German Cancer Society (DKG) (2016) Adherence to granulocyte-colony stimulating factor (G-CSF) guidelines to reduce the incidence of febrile neutropenia after chemotherapy—a representative sample survey in Germany. Support Care Cancer 24:367–376. CrossRefGoogle Scholar
  25. 25.
  26. 26.
    Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379:432–444. CrossRefGoogle Scholar
  27. 27.
    Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717. CrossRefGoogle Scholar
  28. 28.
    Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S, Cardoso F (2015) Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26:v8–v30. CrossRefGoogle Scholar
  29. 29.
    College of Oncology (2013) National clinical practice guidelines: breast cancer version 4.0. Accessed 15 May 2017
  30. 30.
    Steffens C-C, Eschenburg H, Kurbacher C, Goehler T, Schmidt M, Eustermann H, Schaffrik M, Otremba B (2012) Abstract P1-15-02: febrile neutropenia (FN) risk assessment and granulocyte colony-stimulating factor (G-CSF) guideline adherence in patients with breast cancer—results from a German prospective multicentre observational study (PROTECT). Cancer Res 72:P1-15-02 doi:
  31. 31.
    Potosky AL, Malin JL, Kim B, Chrischilles EA, Makgoeng SB, Howlader N, Weeks JC (2011) Use of colony-stimulating factors with chemotherapy: opportunities for cost savings and improved outcomes. J Natl Cancer Inst 103:979–982. CrossRefGoogle Scholar
  32. 32.
    Bennett CL, Smith TJ, Weeks JC, Bredt AB, Feinglass J, Fetting JH, Hillner BE, Somerfield MR, Winn RJ (1996) Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. The Health Services Research Committee of the American Society of Clinical Oncology. J Clin Oncol 14:2511–2520. CrossRefGoogle Scholar
  33. 33.
    Krell D, Jones AL (2009) Impact of effective prevention and management of febrile neutropenia. Br J Cancer 101(Suppl 1):S23–S26. CrossRefGoogle Scholar
  34. 34.
    Barnes G, Pathak A, Schwartzberg L (2014) G-CSF utilization rate and prescribing patterns in United States: associations between physician and patient factors and GCSF use. Cancer Med 3:1477–1484. CrossRefGoogle Scholar
  35. 35.
    Fiegl M, Steger GG, Studnicka M, Eisterer W, Jaeger C, Willenbacher W (2013) Pegfilgrastim prophylaxis in patients at different levels of risk for chemotherapy-associated febrile neutropenia: an observational study. Curr Med Res Opin 29:505–515. CrossRefGoogle Scholar
  36. 36.
    Salar A, Haioun C, Rossi FG, Duehrsen U, Pettengell R, Johnsen HE, Jaeger U, Verhoef G, Schwenkglenks M, Bacon P, Bendall K, Lugtenburg PJ (2012) The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: findings from clinical practice. Leuk Res 36:548–553. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Florence Van Ryckeghem
    • 1
  • Chloë Haverbeke
    • 2
  • Wim Wynendaele
    • 3
  • Guy Jerusalem
    • 4
  • Luc Somers
    • 5
  • Anke Van den broeck
    • 6
  • Sofie Vingerhoedt
    • 6
  • Simon Van Belle
    • 2
    Email author
  1. 1.AZ Glorieux, RonseBelgium and Gent University HospitalGhentBelgium
  2. 2.Gent University HospitalGhentBelgium
  3. 3.Department of Medical OncologyImelda HospitalBonheidenBelgium
  4. 4.CHU Sart Tilman Liège and University of LiègeLiègeBelgium
  5. 5.OncoLogXAntwerpBelgium
  6. 6.AmgenBrusselsBelgium

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