Advertisement

Drugs

, Volume 62, Supplement 1, pp 65–78 | Cite as

Filgrastim in Patients with Neutropenia

Potential Effects on Quality of Life
  • Gary H. LymanEmail author
  • Nicole M. Kuderer
Review Article

Abstract

Treatment- and disease-related neutropenia are associated with a number of negative clinical effects such as febrile neutropenia, documented infection, hospitalisation for infection-related morbidity, infection-related mortality, and decreased ability to administer the planned chemotherapy dose on schedule. Reductions or delays in dosage have the ability to jeopardise the effectiveness of treatment by lowering response rates. Not only are clinical outcomes adversely affected, but these complications can have a negative influence on patient quality of life. Filgrastim is a haematopoietic growth factor that primarily acts to stimulate the proliferation and differentiation of neutrophil progenitor cells. Filgrastim is capable of reducing the incidence and severity of neutropenia and the complications that accompany it in patients with cancer or HIV infection. Although there are few data evaluating the effect of treatment with granulocyte colony-stimulating factor on quality of life, it is assumed that the benefits would be seen through both the reduction of treatment-related complications and the enhanced potential for long-term disease control. A new, longer-acting form of filgrastim is now available that has the potential to simplify the management of neutropenia and further improve patient quality of life by decreasing the number of necessary injections. Additional prospective controlled trials that contain quality-of-life issues as endpoints are needed.

Keywords

Neutropenia Febrile Neutropenia Filgrastim Documented Infection Haematopoietic Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Johnston E, Crawford J. Hematopoietic growth factors in the reduction of chemotherapeutic toxicity. Semin Oncol 1998; 25: 552–651PubMedGoogle Scholar
  2. 2.
    Hermans P, Sommereijns B, Van Cutsem N, et al. Neutropenia in patients with HIV infection: a case control study in a cohort of 1403 patients between 1982 and 1993. J Hematother Stem Cell Res 1999; 8: S23–32PubMedCrossRefGoogle Scholar
  3. 3.
    Hartung T. Granulocyte colony-stimulating factor: its potential role in infectious disease. AIDS 1999; 13: S3–9PubMedGoogle Scholar
  4. 4.
    Frampton JE, Lee CR, Faulds D. Filgrastim: a review of its pharmacological properties and therapeutic efficacy in neutropenia. Drugs 1994; 48: 731–60PubMedCrossRefGoogle Scholar
  5. 5.
    Lyman GH. Economic analysis of cancer clinical trials. In: Crowley J, editor. Handbook of statistics in clinical oncology. New York: Marcel Dekker, 2001: 291–320Google Scholar
  6. 6.
    Muldoon MF, Barger SD, Flory JD, et al. What are quality of life measurements measuring? BMJ 1998; 316: 542–5PubMedCrossRefGoogle Scholar
  7. 7.
    Cella DF, Bonomi AE. Measuring quality of life: 1995 update. Oncology 1995; 9: 47–60PubMedGoogle Scholar
  8. 8.
    Lyman G, Kuderer N. Incorporation of quality-of-life considerations into decision models for the use of colony-stimulating factors in chemotherapy patients at risk for febrile neutropenia. In: Klastersky J, editor. Febrile neutropenia. Heidelberg: Springer Verlag, 1997: 17–22CrossRefGoogle Scholar
  9. 9.
    Dijkers M. Measuring quality of life: methodological issues. Am J Phys Med Rehabil 1999; 78: 286–300PubMedCrossRefGoogle Scholar
  10. 10.
    Pocock SJ, Henderson RA, Clayton T, et al. Quality of life after coronary angioplasty or continued medical treatment for angina: three-year follow-up in the RITA-2 trial: Randomized Intervention Treatment of Angina. J Am Coll Cardiol 2000; 35: 907–14PubMedCrossRefGoogle Scholar
  11. 11.
    Bernhard J, Cella DF, Coates AS, et al. Missing quality of life data in cancer clinical trials: serious problems and challenges. Stat Med 1998; 17(5–7): 517–32PubMedCrossRefGoogle Scholar
  12. 12.
    Macquart-Moulin G, Viens P, Palangie T, et al. High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment? J Clin Oncol 2000; 18: 754–64PubMedGoogle Scholar
  13. 13.
    Ozer H, Armitage JO, Bennett CL, et al. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 2000; 18: 3558–85PubMedGoogle Scholar
  14. 14.
    Stein KD, Jacobson PB, Hann DM, et al. Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer. J Pain Symptom Manage 2000; 19: 436–45PubMedCrossRefGoogle Scholar
  15. 15.
    Swain SM, Rowland J, Weinfurt K, et al. Intensive outpatient adjuvant therapy for breast cancer: results of dose escalation and quality of life. J Clin Oncol 1996; 14: 1565–72PubMedGoogle Scholar
  16. 16.
    Broeckel JA, Jacobson PB, Balducci L, et al. Quality of life after adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 2000; 62: 142–50CrossRefGoogle Scholar
  17. 17.
    Glaspy J, Hackett J, Flyer P, et al. Febrile neutropenia is associated with an increase in the incidence, duration, and severity of chemotherapy toxicities [abstract #1812]. American Society of Hematology; 2001 Dec 7–11; Orlando (FL)Google Scholar
  18. 18.
    Balducci L. Geriatric oncology: challenges for the new century. Eur J Cancer 2000; 36: 1741–54PubMedCrossRefGoogle Scholar
  19. 19.
    Balducci L, Hardy CL, Lyman GH. Hematopoietic growth factors in the older cancer patient. Curr Opin Hematol 2001; 8: 170–87PubMedCrossRefGoogle Scholar
  20. 20.
    Lyman GH, Kuderer NM, Balducci L. Cancer care in the elderly: cost and quality-of-life considerations. Cancer Control 1998; 5: 347–54PubMedGoogle Scholar
  21. 21.
    Balducci L, Lyman GH. Patients aged > or = 70 are at high risk for neutropenic infection and should receive hemopoietic growth factors when treated with moderately toxic chemotherapy. J Clin Oncol 2001; 19: 1583–4PubMedGoogle Scholar
  22. 22.
    Keiser P, Higgs E, Smith J. Neutropenia is associated with bacteremia in patients infected with the human immunodeficiency virus. Am J Med Sci 1996; 312: 118–22PubMedCrossRefGoogle Scholar
  23. 23.
    Kuritzkes DR. Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. Clin Infect Dis 2000; 30: 256–60PubMedCrossRefGoogle Scholar
  24. 24.
    Jacobson MA, Liu RC, Davies D, et al. Human immunodeficiency virus disease-related neutropenia and the risk of hospitalization for bacterial infection. Arch Intern Med 1997; 157: 1825–31PubMedCrossRefGoogle Scholar
  25. 25.
    Remick SC, Sedransk N, Haase RF, et al. Oral combination chemotherapy in conjunction with filgrastim (G-CSF) in the treatment of AIDS-related non-Hodgkin’s lymphoma: evaluation of the role of G-CSF; quality-of-life analysis and long-term follow-up. Am J Hematol 2001; 66: 178–88PubMedCrossRefGoogle Scholar
  26. 26.
    Calhoun EA, Chang C, Welshman EE, et al. Development and validation of the FACT-neutropenia [abstract #1791]; American Society of Hematology; 2001 Dec 7–11; Orlando (FL)Google Scholar
  27. 27.
    Karthaus M, Rosenthal C, Huebner G, et al. Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial. Bone Marrow Transplant 1998; 22: 781–5PubMedCrossRefGoogle Scholar
  28. 28.
    Crawford J, Tomita DK, Mazanet R, et al. Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy. Cytokines Cell Mol Ther 1999; 5: 187–93PubMedGoogle Scholar
  29. 29.
    Sternberg CN, de Mulder PHM, Schornagel JH, et al. Randomized phase III trial of high-dose-intensity methotrexate, vin-blastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer protocol no. 30924. J Clin Oncol 2001; 19: 2638–46PubMedGoogle Scholar
  30. 30.
    Gabrilove JL, Jakubowski A, Scher H, et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional cell carcinoma of the urothelium. N Engl J Med 1988; 318: 1414–22PubMedCrossRefGoogle Scholar
  31. 31.
    Lyman GH. A predictive model for neutropenia associated with cancer chemotherapy. Pharmacotherapy 2000; 20: 104S–11SPubMedCrossRefGoogle Scholar
  32. 32.
    Crawford J, Ozer H, Stoller R. 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
  33. 33.
    Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 3: 319–24CrossRefGoogle Scholar
  34. 34.
    Zinzani PL, Pavone E, Storti S, et al. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin’s lymphoma. Blood 1997; 89: 3974–9PubMedGoogle Scholar
  35. 35.
    Pentengell R, Gurney H, Radford JA, et al. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 1992; 80: 1430–6Google Scholar
  36. 36.
    Lyman GH, Kuderer NM, Djulbegovic B. Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy. Am J Med 2002; 112: 406–11PubMedCrossRefGoogle Scholar
  37. 37.
    Hartmann LC, Tschetter LK, Habermann TM, et al. Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia. N Engl J Med 1997; 336: 1776–80PubMedCrossRefGoogle Scholar
  38. 38.
    Maher D, Lieschke G, Green M, et al. Filgrastim in patients with chemotherapy-induced febrile neutropenia: a double-blind, placebo-controlled trial. Ann Med 1994; 121: 492–501Google Scholar
  39. 39.
    Mitchell PL, Morland B, Stevens MC, et al. Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients. J Clin Oncol 1997; 15: 1163–70PubMedGoogle Scholar
  40. 40.
    Aviles A, Guzman R, Delgado S, et al. Intensive brief chemotherapy with hematopoietic growth factors as hematological support and adjuvant radiotherapy improve the prognosis in aggressive malignant lymphoma. Am J Hematol 1996; 52: 275–80PubMedCrossRefGoogle Scholar
  41. 41.
    Garcia-Carbonero R, Mayordomo JI, Tornamira MV, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J Natl Cancer Inst 2001; 93: 31–8PubMedCrossRefGoogle Scholar
  42. 42.
    Hazel DL, Smith JA, Newland AC, et al. G-CSF increases the efficacy of conventional amphotericin in the treatment of presumed deep-seated fungal infection in neutropenic patients [abstract]. Blood 1996; 88 Suppl. 1: 1692Google Scholar
  43. 43.
    Wingard JR, Elfenbein GJ. Host immunologic augmentation for the control of infection. Infect Dis Clin North Am 1996; 10: 345–64PubMedCrossRefGoogle Scholar
  44. 44.
    Leong KW, Crowley B, White B, et al. Cutaneous mucormycosis due to Absidia corymbifera occurring after bone marrow transplantation. Bone Marrow Transplant 1997; 19: 513–5PubMedCrossRefGoogle Scholar
  45. 45.
    Bouza E, Munoz P, Vega L, et al. Clinical resolution of Scedosporium prolificans fungemia associated with reversal of neutropenia following administration of granulocyte colony-stimulating factor. Clin Infect Dis 1996; 23: 192–3PubMedCrossRefGoogle Scholar
  46. 46.
    Gonzalez CE, Couriel DR, Walsh TJ. Disseminated zygomycosis in a neutropenic patient: successful treatment with amphotericin B lipid complex and granulocyte colony-stimulating factor. Clin Infect Dis 1997; 24: 192–6PubMedCrossRefGoogle Scholar
  47. 47.
    Kern W, Aul C, Maschmeyer G, et al. Granulocyte colony-stimulating factor shortens duration of critical neutropenia and prolongs disease-free survival after sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy for refractory and relapsed acute myeloid leukemia. German AML Cooperative Group. Ann Hematol 1998; 77: 115–22PubMedCrossRefGoogle Scholar
  48. 48.
    Godwin JE, Kopecky KJ, Head DR, et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 1998; 91: 3607–15PubMedGoogle Scholar
  49. 49.
    Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood 1997; 90: 4710–8PubMedGoogle Scholar
  50. 50.
    Larson RA, Dodge RK, Linker CA, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 1998; 92: 1556–64PubMedGoogle Scholar
  51. 51.
    Pui CH, Boyett JM, Hughes WT, et al. Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia. N Engl J Med 1997; 336: 1781–7PubMedCrossRefGoogle Scholar
  52. 52.
    Ottmann OG, Hoelzer D, Gracien E, et al. Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial. Blood 1995; 86: 444–50PubMedGoogle Scholar
  53. 53.
    Weite K, Reiter A, Mempel K, et al. A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Munster Study Group. Blood 1996; 87: 3143–50Google Scholar
  54. 54.
    Geissler K, Koller E, Hubmann E, et al. Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia: a randomized phase-III study. Blood 1997; 90: 590–6PubMedGoogle Scholar
  55. 55.
    Bronchud MH, Howell A, Crowther D, et al. The use of granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer 1989; 60: 121–5PubMedCrossRefGoogle Scholar
  56. 56.
    Thatcher N, Girling DJ, Hopwood P, et al. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol 2000; 18: 395–404PubMedGoogle Scholar
  57. 57.
    Santoro A, Balzarotti M, Tondini C, et al. Dose-escalation of CHOP in non-Hodgkin’s lymphoma. Ann Oncol 1999; 10: 519–25PubMedCrossRefGoogle Scholar
  58. 58.
    Talbot SM, Westerman DA, Grigg AP, et al. Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin’s lymphoma and advanced solid tumors. Ann Oncol 1999; 10: 907–14PubMedCrossRefGoogle Scholar
  59. 59.
    Tanosaki R, Okamoto S, Akatsuka N, et al. Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin’s lymphoma. Cancer 1994; 74: 1939–44PubMedCrossRefGoogle Scholar
  60. 60.
    Vokes EE, Haraf DJ, Mick R, et al. Intensified concomitant chemoradiotherapy with and without filgrastim for poorprognosis head and neck cancer. J Clin Oncol 1994; 12: 2351–9PubMedGoogle Scholar
  61. 61.
    Budd GT, Atiba J, Silver RT, et al. Phase I/II trial of human recombinant granulocyte-colony-stimulating factor (filgrastim) and escalating doses of cyclophosphamide, mitoxantrone, and 5-FU in the treatment of advanced breast cancer. J Cancer Res Clin Oncol 1999; 125: 500–4PubMedCrossRefGoogle Scholar
  62. 62.
    Therasse P, Mauriac L, Weinicka M, et al. An EORTC-NCIC-SAAK neoadjuvant randomized phase III study comparing CEF (5FU, epirubicin, cyclophosphamide) vs dose intensified EC+G-CSF (Filgrastim) in locally advanced breast cancer (LABC) updated results including quality of life [abstract #63P]. Ann Oncol 1998; 9 Suppl. 4Google Scholar
  63. 63.
    Nemunaitis J. A comparative review of colony-stimulating factors. Drugs 1997; 54: 709–29PubMedCrossRefGoogle Scholar
  64. 64.
    Nemunaitis J. Cytokine-mobilized peripheral blood progenitor cells. Semin Oncol 1996; 23: 9–14PubMedGoogle Scholar
  65. 65.
    Costa JJ. The therapeutic use of hematopoietic growth factors. J Allergy Clin Immunol 1998; 101: 1–6PubMedCrossRefGoogle Scholar
  66. 66.
    Schmitz N, Dreger P, Zander AR, et al. Results of a randomised, controlled, multicentre study of recombinant human granulocyte colony-stimulating factor (filgrastim) in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma undergoing autologous bone marrow transplantation. Bone Marrow Transplant 1995; 15: 261–6PubMedGoogle Scholar
  67. 67.
    Weaver CH, Schulman KA, Wilson-Relyea B, et al. Randomized trial of filgrastim, sargramostim, or sequential sargramostim and filgrastim after myelosuppressive chemotherapy for the harvesting of peripheral-blood stem cells. J Clin Oncol 2000; 18: 43–53PubMedGoogle Scholar
  68. 68.
    Schmitz N, Linch DC, Dreger P, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. 1996; 347: 353–7Google Scholar
  69. 69.
    Hengge UR, Brockmeyer NH, Goos M, et al. Granulocyte colony-stimulating factor treatment in AIDS patients. Clin Invest 1992; 70: 922–66CrossRefGoogle Scholar
  70. 70.
    Kimura S, Matsuda J, Ikematsu S, et al. Efficacy of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with AIDS. AIDS 1990; 4: 1251–5PubMedCrossRefGoogle Scholar
  71. 71.
    Mueller BU, Jacobsen F, Butler KM, et al. Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection. J Pediatr 1992; 121: 797–802PubMedCrossRefGoogle Scholar
  72. 72.
    Kuritzkes DR, Parenti D, Ward DJ, et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group. AIDS 1998; 12: 65–74PubMedCrossRefGoogle Scholar
  73. 73.
    Hermans P, Franchioly P, Thioux C, et al. Minimum effective dose and duration to reverse neutropenia in non-cancer patients with advanced HIV disease. AIDS 1996; 10: 350–1CrossRefGoogle Scholar
  74. 74.
    Nielsen SD, Sorensen TU, Aladdin H, et al. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals. Scand J Immunol 2000; 52: 298–303PubMedCrossRefGoogle Scholar
  75. 75.
    Miles SA, Mitsuyasu RT, Moreno J, et al. Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine. Blood 1991; 77: 2109–17PubMedGoogle Scholar
  76. 76.
    Keiser P, Rademacher S, Smith J, et al. G-CSF association with prolonged survival in HIV-infected patients with disseminated Mycobacterium avium. complex infection. Int J STD AIDS 1998; 9: 394–9PubMedCrossRefGoogle Scholar
  77. 77.
    Seidman AD, Portenoy R, Yao TJ, et al. Quality of life in phase II trials: a study of methodology and predictive value in patients with advanced breast cancer treated with paclitaxel plus granulocyte colony-stimulating factor. J Natl Cancer Inst 1995; 87: 1316–22PubMedCrossRefGoogle Scholar
  78. 78.
    Jones EA, Bolyard AA, Dale DC. Quality of life of patients with severe chronic neutropenia receiving long-term treatment with granulocyte colony-stimulating factor. JAMA 1993; 270: 1132–3PubMedCrossRefGoogle Scholar
  79. 79.
    Fazio MT, Glaspy JA. The impact of granulocyte colony-stimulating factor on quality of life in patients with severe chronic neutropenia. Oncol Nurs Forum 1991; 18: 1411–4PubMedGoogle Scholar
  80. 80.
    Johnston E, Crawford J, Blackwell S, et al. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 2000; 18: 2522–8PubMedGoogle Scholar
  81. 81.
    Holmes FA, O’Shaughnessy JA, Vukelja S, et al. A single dose of pegylated filgrastim (SD/01) is as effective as daily filgrastim for hematologic support of chemotherapy in breast cancer patients: results of a randomized, double-blind, phase 3 trial [abstract #27]. Proceedings of the 37 th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San Francisco (CA)Google Scholar
  82. 82.
    Green M, Koelbl H, Baselga J, et al. A randomized, double-blind, phase 3 study evaluating fixed-dose, once-per-cycle pegylated filgrastim (SD/01) vs daily filgrastim to support chemotherapy for breast cancer [abstract #90]. Proceedings of the 37th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San Francisco (CA)Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Health Services and Outcomes Research Program, James P. Wilmot Cancer CenterUniversity of Rochester Medical CenterRochesterUSA

Personalised recommendations