Myeloid Growth Factors Clinical Practice Guidelines in OncologyNCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).Category 3: The recommendation is based on any level of evidence but reflects major disagreement.All recommendations are category 2A unless otherwise noted.Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.OverviewNeutropenia (< 500 neutrophils/mcL or < 1000 neutrophils/mcL and a predicted decline to ≤ 500/mcL over the next 48 hours) and resulting febrile neutropenia (FN; ≥ 38.3°C orally or ≥ 38.0°C over 1 hour) can be induced by myelosuppressive chemotherapy. FN is a major dose-limiting toxicity of chemotherapy, often necessitating hospitalization for evaluation and empiric broad-spectrum antibiotics. These complications often result in dose reductions or treatment delays, which may compromise clinical outcomes. The prophylactic use of colony-stimulating factors (CSFs) can reduce the risk, severity, and duration of FN. Despite these benefits, CSFs are not administered to all patients under going myelosuppressive chemotherapy because of the costs associated with routine use. Selective use of CSFs in patients at increased risk for neutropenic complications may, however, enhance cost-effectiveness by directing treatment toward patients most likely to...

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  • 1

    DaleDCMcCarterGCCrawfordJ. Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials. J Natl Compr Canc Netw2003;1:440454.

    • Search Google Scholar
    • Export Citation
  • 2

    DaleDC. Colony-stimulating factors for the management of neutropenia in cancer patients. Drugs2002;62(Suppl 1):115.

  • 3

    LymanGHKudererNM. Filgrastim in patients with neutropenia: potential effects on quality of life. Drugs2002;62(Suppl 1):6578.

  • 4

    GisselbrechtCHaiounCLepageE. Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin’s lymphoma: factors influencing chemotherapy administration. Groupe d’Etude des Lymphomes de l’Adulte. Leuk Lymphoma1997;25:289300.

    • Search Google Scholar
    • Export Citation
  • 5

    Timmer-BonteJNde BooTMSmitHJ. Prevention of chemotherapy-induced febrile neutropenia by prophylactic antibiotics plus or minus granulocyte colony-stimulating factor in small-cell lung cancer: a Dutch randomized phase III study. J Clin Oncol2005;23:79747984.

    • Search Google Scholar
    • Export Citation
  • 6

    Trillet-LenoirVGreenJManegoldC. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer1993;29A:319324.

    • Search Google Scholar
    • Export Citation
  • 7

    VogelCLWojtukiewiczMZCarrollRR. 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 Oncol2005;23:11781184.

    • Search Google Scholar
    • Export Citation
  • 8

    BuiBNChevallierBChevreauC. Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity. J Clin Oncol1995;13:26292636.

    • Search Google Scholar
    • Export Citation
  • 9

    ChevallierBCholletPMerroucheY. Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer. J Clin Oncol1995;13:15641571.

    • Search Google Scholar
    • Export Citation
  • 10

    CrawfordJOzerHStollerR. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med1991;325:164170.

    • Search Google Scholar
    • Export Citation
  • 11

    GatzemeierUKleisbauerJPDringsP. Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase III, multicenter, randomized study. Am J Clin Oncol2000;23:393400.

    • Search Google Scholar
    • Export Citation
  • 12

    MuhonenTJantunenIPertovaaraH. Prophylactic filgrastim (G-CSF) during mitomycin-C, mitoxantrone, and methotrexate (MMM) treatment for metastatic breast cancer. A randomized study. Am J Clin Oncol1996;19:232234.

    • Search Google Scholar
    • Export Citation
  • 13

    OsbyEHagbergHKvaloyS. CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial. Blood2003;101:38403848.

    • Search Google Scholar
    • Export Citation
  • 14

    PettengellRGurneyHRadfordJA. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood1992;80:14301436.

    • Search Google Scholar
    • Export Citation
  • 15

    ZinzaniPLPavoneEStortiS. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin’s lymphoma. Blood1997;89:39743979.

    • Search Google Scholar
    • Export Citation
  • 16

    DoorduijnJKvan der HoltBvan ImhoffGW. CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin’s lymphoma. J Clin Oncol2003;21:30413050.

    • Search Google Scholar
    • Export Citation
  • 17

    FossaSDKayeSBMeadGM. Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. J Clin Oncol1998;16:716724.

    • Search Google Scholar
    • Export Citation
  • 18

    CitronMLBerryDACirrincioneC. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol2003;21:14311439.

    • Search Google Scholar
    • Export Citation
  • 19

    PfreundschuhMTrumperLKloessM. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood2004;104:634641.

    • Search Google Scholar
    • Export Citation
  • 20

    BohliusJReiserMSchwarzerGEngertA. Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev2004:CD003189.

    • Search Google Scholar
    • Export Citation
  • 21

    SungLNathanPCAlibhaiSM. Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med2007;147:400411.

    • Search Google Scholar
    • Export Citation
  • 22

    ClarkOALymanGHCastroAA. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol2005;23:41984214.

    • Search Google Scholar
    • Export Citation
  • 23

    KudererNMDaleDCCrawfordJLymanGH. 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 Oncol2007;25:31583167.

    • Search Google Scholar
    • Export Citation
  • 24

    LymanGHKudererNM. The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia. Crit Rev Oncol Hematol2004;50:129146.

    • Search Google Scholar
    • Export Citation
  • 25

    CoslerLEEldar-LissaiACulakovaE. Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective. Pharmacoeconomics2007;25:343351.

    • Search Google Scholar
    • Export Citation
  • 26

    DoorduijnJKBuijtIvan der HoltB. Economic evaluation of prophylactic granulocyte colony stimulating factor during chemotherapy in elderly patients with aggressive non-Hodgkin’s lymphoma. Haematologica2004;89:11091117.

    • Search Google Scholar
    • Export Citation
  • 27

    Eldar-LissaiACoslerLECulakovaELymanGH. Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy. Value Health2008;11:172179.

    • Search Google Scholar
    • Export Citation
  • 28

    NumnumTMKimballKJRocconiRP. Pegfilgrastim for the prevention of febrile neutropenia in patients with epithelial ovarian carcinoma—a cost-effectiveness analysis. Int J Gynecol Cancer2007;17:10191024.

    • Search Google Scholar
    • Export Citation
  • 29

    Timmer-BonteJNAdangEMTermeerE. Modeling the cost effectiveness of secondary febrile neutropenia prophylaxis during standard-dose chemotherapy. J Clin Oncol2008;26:290296.

    • Search Google Scholar
    • Export Citation
  • 30

    U.S. Food and Drug Administration. FDA filgrastim and pegfilgrastim labels.Available at: http://www.fda.gov/cder/foi/label/2006/103353s5086LBL.pdf and http://www.fda.gov/cder/foi/label/2007/125031s082lbl.pdf. Accessed October 29 2008.

    • Search Google Scholar
    • Export Citation
  • 31

    MartinWGRistowKMHabermannTM. Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin’s lymphoma. J Clin Oncol2005;23:76147620.

    • Search Google Scholar
    • Export Citation
  • 32

    TigueCCMcKoyJMEvensAM. Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant2007;40:185192.

    • Search Google Scholar
    • Export Citation
  • 33

    AaproMSCameronDAPettengellR. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer2006;42:24332453.

    • Search Google Scholar
    • Export Citation
  • 34

    SmithTJKhatcheressianJLymanGH. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol2006;24:31873205.

    • Search Google Scholar
    • Export Citation
  • 35

    CrawfordJDaleDCLymanGH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer2004;100:228237.

    • Search Google Scholar
    • Export Citation
  • 36

    LymanGH. Risk assessment in oncology clinical practice. From risk factors to risk models. Oncology (Williston Park)2003;17:813.

  • 37

    AzoulayEAttalahHHarfA. Granulocyte colony-stimulating factor or neutrophil-induced pulmonary toxicity: myth or reality? Systematic review of clinical case reports and experimental data. Chest2001;120:16951701.

    • Search Google Scholar
    • Export Citation
  • 38

    EvensAMCilleyJOrtizT. G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis. Br J Haematol2007;137:545552.

    • Search Google Scholar
    • Export Citation
  • 39

    LymanGHLymanCHAgboolaO. Risk models for predicting chemotherapy-induced neutropenia. Oncologist2005;10:427437.

  • 40

    AslaniASmithRCAllenBJ. The predictive value of body protein for chemotherapy-induced toxicity. Cancer2000;88:796803.

  • 41

    ChrischillesEDelgadoDJStolshekBS. Impact of age and colony-stimulating factor use on hospital length of stay for febrile neutropenia in CHOP-treated non-Hodgkin’s lymphoma. Cancer Control2002;9:203211.

    • Search Google Scholar
    • Export Citation
  • 42

    LymanGHDelgadoDJ. Risk and timing of hospitalization for febrile neutropenia in patients receiving CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma. Cancer2003;98:24022409.

    • Search Google Scholar
    • Export Citation
  • 43

    LymanGHMorrisonVADaleDC. Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma2003;44:20692076.

    • Search Google Scholar
    • Export Citation
  • 44

    MorrisonVAPicozziVScottS. The impact of age on delivered dose intensity and hospitalizations for febrile neutropenia in patients with intermediate-grade non-Hodgkin’s lymphoma receiving initial CHOP chemotherapy: a risk factor analysis. Clin Lymphoma2001;2:4756.

    • Search Google Scholar
    • Export Citation
  • 45

    LymanGHDaleDCCrawfordJ. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol2003;21: 45244531.

    • Search Google Scholar
    • Export Citation
  • 46

    LymanGHDaleDCFriedbergJ. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol2004;22:43024311.

    • Search Google Scholar
    • Export Citation
  • 47

    BerghmansTPaesmansMLafitteJJ. Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer2002;10:181188.

    • Search Google Scholar
    • Export Citation
  • 48

    Garcia-CarboneroRMayordomoJITornamiraMV. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst2001;93:3138.

    • Search Google Scholar
    • Export Citation
  • 49

    JohnstonECrawfordJBlackwellS. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol2000;18:25222528.

    • Search Google Scholar
    • Export Citation
  • 50

    CrawfordJ. Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia. Semin Oncol2003;30:2430.

  • 51

    LokichJJ. Same day pegfilgrastim and CHOP chemotherapy for non-Hodgkin lymphoma. Am J Clin Oncol2006;29:361363.

  • 52

    KaufmanPAParolyWRinaldiD. Randomized double blind phase 2 study evaluating same-day vs. next-day administration of pegfilgrastim with docetaxel, doxorubicin and cyclophosphamide (TAC) in women with early stage and advanced breast cancer SABCS [abstract]. Breast Cancer Res Treat2004;88:Abstract 1054.

    • Search Google Scholar
    • Export Citation
  • 53

    BelaniCPRamalingamSAl-JanadiA. A randomized double-blind phase II study to evaluate same-day vs next-day administration of pegfilgrastim with carboplatin and docetaxel in patients with NSCLC [abstract]. J Clin Oncol2006;24(Suppl 1):Abstract 7110.

    • Search Google Scholar
    • Export Citation
  • 54

    StullDMBilmesRKimHFichtlR. Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm2005;62:8387.

    • Search Google Scholar
    • Export Citation
  • 55

    DaleDCBonillaMADavisMW. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood1993;81:24962502.

    • Search Google Scholar
    • Export Citation
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