Journal Article
. 2014 Apr; 14:189.
doi: 10.1186/1472-6963-14-189.

Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis

Derek Weycker 1 Rich Barron  John Edelsberg  Alex Kartashov  Jason Legg  Andrew G Glass  
  • PMID: 24767095
  •     29 References
  •     10 citations


Background: To examine duration of daily filgrastim prophylaxis, and risk and consequences of chemotherapy-induced neutropenic complications (CINC) requiring inpatient care.

Methods: Using a retrospective cohort design and US healthcare claims data (2001-2010), we identified all cancer patients who initiated ≥1 course of myelosuppressive chemotherapy and received daily filgrastim prophylactically in ≥1 cycle. Cycles with daily filgrastim prophylaxis were pooled for analyses. CINC was identified based on hospital admissions with a diagnosis of neutropenia, fever, or infection; consequences were characterized in terms of hospital mortality, hospital length of stay (LOS), and CINC-related healthcare expenditures.

Results: Risk of CINC requiring inpatient care-adjusted for patient characteristics-was 2.4 (95% CI: 1.6-3.4) and 1.9 (1.3-2.8) times higher with 1-3 (N = 8371) and 4-6 (N = 3691) days of filgrastim prophylaxis, respectively, versus ≥7 days (N = 2226). Among subjects who developed CINC, consequences with 1-3 and 4-6 (vs. ≥7) days of filgrastim prophylaxis were: mortality (8.4% [n/N = 10/119] and 4.0% [3/75] vs. 0% [0/34]); LOS (means: 7.4 [N = 243] and 7.1 [N = 99] vs. 6.5 [N = 40]); and expenditures (means: $18,912 [N = 225] and $14,907 [N = 94] vs. $13,165 [N = 39]).

Conclusions: In this retrospective evaluation, shorter courses of daily filgrastim prophylaxis were found to be associated with an increased risk of CINC as well as poorer outcomes among those developing this condition. Because of the limitations inherent in healthcare claims databases specifically and retrospective evaluations generally, additional research addressing these limitations is needed to confirm the findings of this study.

Observational study of the prevalence of febrile neutropenia in patients who received filgrastim or pegfilgrastim associated with 3-4 week chemotherapy regimens in community oncology practices.
Vicki A Morrison, Mitchell Wong, +3 authors, Jennifer Malin.
J Manag Care Pharm, 2007 May 18; 13(4). PMID: 17506600
Trends in recommendations for myelosuppressive chemotherapy for the treatment of solid tumors.
Robert E Smith.
J Natl Compr Canc Netw, 2006 Aug 04; 4(7). PMID: 16884668
Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim.
Lodovico Balducci, Hafez Al-Halawani, +4 authors, William B Ershler.
Oncologist, 2008 Jan 01; 12(12). PMID: 18165618
Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP.
A Bosly, D Bron, +6 authors, G Verhoef.
Ann Hematol, 2007 Oct 24; 87(4). PMID: 17952688
Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis: a retrospective cohort study.
Derek Weycker, Jennifer Malin, +4 authors, Gerry Oster.
Clin Ther, 2009 Jun 23; 31(5). PMID: 19539108
A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy.
J Randolph Hecht, Madhavan Pillai, +6 authors, Imtiaz Malik.
Clin Colorectal Cancer, 2010 Apr 10; 9(2). PMID: 20378503
Comparative effectiveness of white blood cell growth factors on neutropenia, infection, and survival in older people with non-Hodgkin's lymphoma treated with chemotherapy.
Stephen K Gruschkus, David Lairson, +2 authors, Xianglin L Du.
J Am Geriatr Soc, 2010 Sep 16; 58(10). PMID: 20840455    Free PMC article.
Risk of mortality in patients with cancer who experience febrile neutropenia.
Gary H Lyman, Shannon L Michels, +3 authors, Jingbo Yu.
Cancer, 2010 Aug 18; 116(23). PMID: 20715160
Comparative effectiveness of colony-stimulating factors for febrile neutropenia: a retrospective study.
Hiangkiat Tan, Karen Tomic, +3 authors, Jen Malin.
Curr Med Res Opin, 2010 Nov 26; 27(1). PMID: 21091127
Effect of primary prophylactic granulocyte-colony stimulating factor use on incidence of neutropenia hospitalizations for elderly early-stage breast cancer patients receiving chemotherapy.
Suja S Rajan, Gary H Lyman, Sally C Stearns, William R Carpenter.
Med Care, 2011 Apr 12; 49(7). PMID: 21478779
Incidence of reduced chemotherapy relative dose intensity among women with early stage breast cancer in US clinical practice.
Derek Weycker, Rich Barron, +2 authors, Gary H Lyman.
Breast Cancer Res Treat, 2012 Jan 25; 133(1). PMID: 22270932
A way forward on the medically appropriate use of white cell growth factors.
Thomas J Smith, Bruce E Hillner.
J Clin Oncol, 2012 Mar 01; 30(14). PMID: 22370327    Free PMC article.
Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim as prophylaxis against hospitalization for neutropenic complications in patients with cancer receiving chemotherapy.
Derek Weycker, Jennifer Malin, +3 authors, Gerry Oster.
Am J Clin Oncol, 2011 Mar 08; 35(3). PMID: 21378538
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.
F A Holmes, J A O'Shaughnessy, +10 authors, B C Liang.
J Clin Oncol, 2002 Feb 01; 20(3). PMID: 11821454
Impact of age and colony-stimulating factor use on hospital length of stay for febrile neutropenia in CHOP-treated non-Hodgkin's lymphoma.
Elizabeth Chrischilles, David J Delgado, +3 authors, William B Carter.
Cancer Control, 2002 Jun 13; 9(3). PMID: 12060818
A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.
M D Green, H Koelbl, +12 authors, International Pegfilgrastim 749 Study Group.
Ann Oncol, 2002 Dec 19; 14(1). PMID: 12488289
Highly Cited.
Quality of well-being in older people with osteoarthritis.
Erik J Groessl, Robert M Kaplan, Terry A Cronan.
Arthritis Rheum, 2003 Feb 13; 49(1). PMID: 12579590
Days of prophylactic filgrastim use to reduce febrile neutropenia in patients with non-Hodgkin's lymphoma treated with chemotherapy.
Shane D Scott, Elizabeth A Chrischilles, +3 authors, Bradley S Stolshek.
J Manag Care Pharm, 2003 Nov 14; 9(2 Suppl). PMID: 14613340
Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.
Gary H Lyman, David C Dale, Jeffrey Crawford.
J Clin Oncol, 2003 Dec 16; 21(24). PMID: 14673039
Highly Cited.
Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.
L W Kwak, J Halpern, R A Olshen, S J Horning.
J Clin Oncol, 1990 Jun 01; 8(6). PMID: 2348230
Highly Cited.
Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer.
J Crawford, H Ozer, +7 authors, G Rausch.
N Engl J Med, 1991 Jul 18; 325(3). PMID: 1711156
Highly Cited.
30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study.
Gianni Bonadonna, Angela Moliterni, +4 authors, Pinuccia Valagussa.
BMJ, 2005 Jan 15; 330(7485). PMID: 15649903    Free PMC article.
First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study.
Charles L Vogel, Marek Z Wojtukiewicz, +5 authors, Lee S Schwartzberg.
J Clin Oncol, 2005 Feb 19; 23(6). PMID: 15718314
Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy.
Vincent Caggiano, Richard V Weiss, Timothy S Rickert, Walter T Linde-Zwirble.
Cancer, 2005 Mar 08; 103(9). PMID: 15751024
Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization?
Derek Weycker, James Hackett, +2 authors, Andrew G Glass.
Ann Pharmacother, 2006 Feb 24; 40(3). PMID: 16492793
Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients.
Nicole M Kuderer, David C Dale, +2 authors, Gary H Lyman.
Cancer, 2006 Apr 01; 106(10). PMID: 16575919
Highly Cited.
Trends in recommendations of myelosuppressive chemotherapy for the treatment of breast cancer: evolution of the national comprehensive cancer network guidelines and the cooperative group studies.
Edgardo Rivera, Robert E Smith.
Clin Breast Cancer, 2006 Jun 13; 7(1). PMID: 16764742
2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.
Thomas J Smith, James Khatcheressian, +19 authors, Antonio C Wolff.
J Clin Oncol, 2006 May 10; 24(19). PMID: 16682719
Highly Cited.
Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: a randomized phase 2 trial.
G Romieu, M Clemens, +7 authors, W Brugger.
Crit Rev Oncol Hematol, 2007 Feb 24; 64(1). PMID: 17317205
Characteristic clinical features of Aspergillus appendicitis: Case report and literature review.
Mihajlo Gjeorgjievski, Mitual B Amin, Mitchell S Cappell.
World J Gastroenterol, 2015 Dec 08; 21(44). PMID: 26640349    Free PMC article.
G-CSF use in patients receiving first-line chemotherapy for non-Hodgkin's lymphoma (NHL) and granulocyte-colony stimulating factors (G-CSF) as observed in clinical practice in Italy.
Umberto Vitolo, Francesco Angrili, +2 authors, Massimo Federico.
Med Oncol, 2016 Nov 09; 33(12). PMID: 27822615
Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.
T Christopher Bond, Erika Szabo, +5 authors, Boxiong Tang.
J Oncol Pharm Pract, 2017 Jun 16; 24(6). PMID: 28614980    Free PMC article.
Profiling chemotherapy-associated myelotoxicity among Chinese gastric cancer population receiving cytotoxic conventional regimens: epidemiological features, timing, predictors and clinical impacts.
Ci Zhu, Yan Wang, +4 authors, Jianming Xu.
J Cancer, 2017 Sep 14; 8(13). PMID: 28900499    Free PMC article.
Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy.
Kalpna Desai, Priya Misra, Sanyukta Kher, Nirmesh Shah.
Exp Hematol Oncol, 2018 Sep 12; 7. PMID: 30202638    Free PMC article.
Incidence of febrile neutropenia during chemotherapy among patients with nonmyeloid cancer receiving filgrastim vs a filgrastim biosimilar.
Lee S Schwartzberg, Lincy S Lal, +4 authors, Stephanie Korrer.
Clinicoecon Outcomes Res, 2018 Sep 15; 10. PMID: 30214262    Free PMC article.
Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia.
Paul Cornes, Pere Gascon, +5 authors, Luiz H Arantes.
Adv Ther, 2018 Oct 10; 35(11). PMID: 30298233    Free PMC article.
Systematic Review.
Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure.
Paul Cornes, Pere Gascon, Arnold G Vulto, Matti Aapro.
BioDrugs, 2020 Apr 02; 34(3). PMID: 32232676    Free PMC article.
Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC).
Mark Clemons, Sasha Mazzarello, +12 authors, Dean Fergusson.
Support Care Cancer, 2018 Aug 14; 27(4). PMID: 30099602
A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia.
Mark Clemons, Dean Fergusson, +18 authors, REThinking Clinical Trials (REaCT) investigators.
Breast, 2021 Apr 27; 58. PMID: 33901921    Free PMC article.