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Medical Oncology

, 32:236 | Cite as

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

  • Gilles FreyerEmail author
  • Ewa Kalinka-Warzocha
  • Konstantinos Syrigos
  • Mihai Marinca
  • Giuseppe Tonini
  • Say Liang Ng
  • Zee Wan Wong
  • Antonio Salar
  • Guenther Steger
  • Mahmoud Abdelsalam
  • Lucy DeCosta
  • Zsolt Szabo
Original Paper

Abstract

Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy. This prospective, observational study describes physicians’ approaches toward assessing FN risk in patients receiving chemotherapy regimens with an intermediate (10–20 %) FN risk. In the baseline investigator assessment, physicians selected factors considered important when assessing overall FN risk and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP). Physicians then completed patient assessments using the same lists of factors. The final FN risk scores and whether G-CSF PP was planned were reported. The final analysis included 165 physicians and 944 patients. The most frequently considered factor in both assessments was chemotherapy agents in the backbone (88 % of investigator and 93 % of patient assessments). History of FN (83 %), baseline laboratory values (76 %) and age (73 %) were commonly selected at baseline, whereas tumor type (72 %), guidelines (62 %) and tumor stage (43 %) were selected most during patient assessments. Median investigator-reported FN risk threshold for G-CSF PP was 20 % (range 10–85 %). G-CSF PP was planned in 82 % of patients with an FN risk at or above this threshold; therefore, almost one-fifth of qualifying patients would not receive G-CSF PP. Physicians generally follow guidelines, but also consider individual patient characteristics when assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may optimize the use of G-CSF PP, which may minimize the incidence of FN in patients undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov Identifier: NCT01813721.

Keywords

Febrile neutropenia Chemotherapy Granulocyte colony-stimulating factor G-CSF Prophylaxis Risk factors 

Notes

Acknowledgments

This study was sponsored by Amgen. We thank all patients, physicians, coordinators and other staff who participated in the study. Medical writing support was provided by Elizabeth Hartfield (Ph.D.) from Oxford PharmaGenesis, Oxford, UK. Funding for this support was provided by Amgen (Europe) GmbH.

Compliance with ethical standards

Conflicts of interest

Gilles Freyer, Giuseppe Tonini, Konstantinos Syrigos, Zee Wan Wong, Say Liang Ng and Antonio Salar have declared no conflicts of interest. Ewa Kalinka-Warzocha has received honoraria from Amgen and Teva. Mihai Marinca has received honoraria from Amgen and Sandoz. Guenther Steger has received honoraria from and has participated in advisory board meetings for Amgen and Teva. Mahmood Abdelsalam has received consultancy fees from Sanofi and honoraria from Eli Lilly and Johnson & Johnson. He has also received travel grants from Amgen, Roche and Astellas and has participated in advisory board meetings for Amgen, Janssen and Innomar Strategies. Lucy DeCosta and Zsolt Szabo are employees and shareholders of Amgen.

Supplementary material

12032_2015_682_MOESM1_ESM.docx (140 kb)
Supplementary material 1 (DOCX 139 kb)

References

  1. 1.
    Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis. 2005;40(Suppl 4):S240–5.CrossRefPubMedGoogle Scholar
  2. 2.
    de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, Roila F. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21(Suppl 5):v252–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Okera M, Chan S, Dernede U, Larkin J, Popat S, Gilbert D, et al. A prospective study of chemotherapy-induced febrile neutropenia in the South West London Cancer Network. Interpretation of study results in light of NCAG/NCEPOD findings. Br J Cancer. 2011;104:407–12.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Schelenz S, Giles D, Abdallah S. Epidemiology, management and economic impact of febrile neutropenia in oncology patients receiving routine care at a regional UK cancer centre. Ann Oncol. 2012;23:1889–93.CrossRefPubMedGoogle Scholar
  5. 5.
    Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106:2258–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Khan S, Dhadda A, Fyfe D, Sundar S. Impact of neutropenia on delivering planned chemotherapy for solid tumours. Eur J Cancer Care (Engl). 2008;17:19–25.Google Scholar
  7. 7.
    Pettengell R, Gurney H, Radford JA, Deakin DP, James R, Wilkinson PM, et al. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood. 1992;80:1430–6.PubMedGoogle Scholar
  8. 8.
    Pettengell R, Schwenkglenks M, Leonard R, Bosly A, Paridaens R, Constenla M, et al. Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study. Support Care Cancer. 2008;16:1299–309.CrossRefPubMedGoogle Scholar
  9. 9.
    Budman DR, Berry DA, Cirrincione CT, Henderson IC, Wood WC, Weiss RB, et al. Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst. 1998;90:1205–11.CrossRefPubMedGoogle Scholar
  10. 10.
    French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2001;19:602–11.Google Scholar
  11. 11.
    Wildiers H, Reiser M. Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol. 2011;77:221–40.CrossRefPubMedGoogle Scholar
  12. 12.
    Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL. Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer. 2011;11:404.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I, 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;325:164–70.CrossRefPubMedGoogle Scholar
  14. 14.
    Pfeil AM, Allcott K, Pettengell R, von Minckwitz G, Schwenkglenks M, Szabo Z. Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review. Support Care Cancer. 2014;23:525–45.CrossRefPubMedGoogle Scholar
  15. 15.
    Pinter T, Abella S, Cesas A, Croitoru A, Decaestecker J, Gibbs P, et al. Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC). J Clin Oncol. 2013;30:LBA445.Google Scholar
  16. 16.
    Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, et al. 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. 2005;23:1178–84.CrossRefPubMedGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    von Minckwitz G, Schwenkglenks M, Skacel T, Lyman GH, Pousa AL, Bacon P, et al. Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: results from an integrated analysis. Eur J Cancer. 2009;45:608–17.CrossRefGoogle Scholar
  19. 19.
    Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, et al. The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2013;24:2475–84.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, et al. 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. 2010;2011(47):8–32.Google Scholar
  21. 21.
    Crawford J, Caserta C, Roila F. Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications. Ann Oncol. 2010;21(Suppl 5):v248–51.CrossRefPubMedGoogle Scholar
  22. 22.
    National Comprehensive Cancer Network. 2006 Update of ASCO practice guideline recommendations for the use of white blood cell growth factors: guideline summary V.1.2010. NCCN Clinical Practice Guidelines in Oncology. 2010. http://jhasioncology.com/fn2010/eresourcecenter/pdfs/NCCN%20myeloid_growth%20factor%20guidelines.%20v1.2010.pdf. Accessed 30 Jan 2015.
  23. 23.
    National Comprehensive Cancer Network. Prevention and treatment of cancer-related infections V.1.2013. NCCN Clinical Practice Guidelines in Oncology. 2013. http://oralcancerfoundation.org/treatment/pdf/infections.pdf. Accessed 30 Jan 2015.
  24. 24.
    Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10:427–37.CrossRefPubMedGoogle Scholar
  25. 25.
    Jha A. Spectrum of hematological malignancies and peripheral cytopenias. J Nepal Health Res Counc. 2013;11:273–8.PubMedGoogle Scholar
  26. 26.
    National Cancer Institute. SEER cancer statistics review 1975–2003. http://seer.cancer.gov/archive/csr/1975_2003/results_single/sect_01_table.11_2pgs.pdf. Accessed 30 Jan 2015.
  27. 27.
    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.CrossRefPubMedGoogle Scholar
  28. 28.
    Falandry C, Campone M, Cartron G, Guerin D, Freyer G. Trends in G-CSF use in 990 patients after EORTC and ASCO guidelines. Eur J Cancer. 2010;46:2389–98.CrossRefPubMedGoogle Scholar
  29. 29.
    Chan A, Verma S, Loibl S, Crawford J, Choi MR, Dreiling L, et al. Reporting of myelotoxicity associated with emerging regimens for the treatment of selected solid tumors. Crit Rev Oncol Hematol. 2012;81:136–50.CrossRefPubMedGoogle Scholar
  30. 30.
    Dale DC, McCarter GC, Crawford J, Lyman GH. Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. J Natl Compr Canc Netw. 2003;1:440–54.PubMedGoogle Scholar
  31. 31.
    Gregory SAAS, Moore T. Underreporting of neutropenic toxicity associated with current treatment regimens for selected hematologic malignancies. Commun Oncol. 2011;8:311–25.CrossRefGoogle Scholar
  32. 32.
    Madarnas Y, Dent SF, Husain SF, Robinson A, Alkhayyat S, Hopman WM, et al. Real-world experience with adjuvant FEC-D chemotherapy in four Ontario regional cancer centres. Curr Oncol. 2011;18:119–25.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Younis T, Rayson D, Thompson K. Primary G-CSF prophylaxis for adjuvant TC or FEC-D chemotherapy outside of clinical trial settings: a systematic review and meta-analysis. Support Care Cancer. 2012;20:2523–30.CrossRefPubMedGoogle Scholar
  34. 34.
    O’Brien C, Dempsey O, Kennedy MJ. Febrile neutropenia risk assessment tool: improving clinical outcomes for oncology patients. Eur J Oncol Nurs. 2014;18:167–74.CrossRefPubMedGoogle Scholar
  35. 35.
    Vavra KL, Saadeh CE, Rosen AL, Uptigrove CE, Srkalovic G. Improving the relative dose intensity of systemic chemotherapy in a community-based outpatient cancer center. J Oncol Pract. 2013;9:e203–11.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gilles Freyer
    • 1
    Email author
  • Ewa Kalinka-Warzocha
    • 2
  • Konstantinos Syrigos
    • 3
  • Mihai Marinca
    • 4
  • Giuseppe Tonini
    • 5
  • Say Liang Ng
    • 6
  • Zee Wan Wong
    • 7
  • Antonio Salar
    • 8
  • Guenther Steger
    • 9
  • Mahmoud Abdelsalam
    • 10
  • Lucy DeCosta
    • 11
  • Zsolt Szabo
    • 12
  1. 1.Department of Medical Oncology, Hospices Civils de Lyon Cancer InstituteLyon UniversityLyonFrance
  2. 2.Chemotherapy DepartmentProvincial Specialist HospitalLodzPoland
  3. 3.Sotiria General HospitalUniversity of Athens Medical SchoolAthensGreece
  4. 4.Department of Oncology, Faculty of MedicineUniversity of Medicine and Pharmacy ‘Grigore T Popa’IasiRomania
  5. 5.Department of OncologyCampus Bio-Medico University of RomeRomeItaly
  6. 6.Oncology UnitBendigo Health Care GroupBendigoAustralia
  7. 7.Oncology Unit, Goulburn Valley Health, SheppartonUniversity of MelbourneMelbourneAustralia
  8. 8.Department of Clinical HaematologyHospital del MarBarcelonaSpain
  9. 9.Department of Internal Medicine I/OncologyMedical University of ViennaViennaAustria
  10. 10.Medical OncologyThe Moncton HospitalMonctonCanada
  11. 11.Amgen LtdUxbridgeUK
  12. 12.Amgen (Europe) GmbHZugSwitzerland

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