Skip to main content
SpringerLink
Log in

Pegfilgrastim Administered Once Per Cycle Reduces Incidence of Chemotherapy-Induced Neutropenia

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Neutropenia is a common and potentially dangerous adverse effect of cancer chemotherapy. It also often necessitates a reduction or delay in dose, thus compromising efficacy. The human granulocyte colony-stimulating factor filgrastim has been proven to have a good safety profile and to be effective in accelerating neutrophil recovery and reducing the incidence of infections following myelosuppressive chemotherapy. However, its short serum half-life necessitates daily administration. Pegylated filgrastim (pegfilgrastim) was developed by attaching a polyethylene glycol moiety to the filgrastim protein. Pegfilgrastim binds to the same cell surface receptor on neutrophils and their precursors as filgrastim and stimulates the proliferation and differentiation of neutrophils through the same mechanism. However, because of the pegylation, it is minimally cleared by the kidneys and has a much longer serum half-life. Furthermore, its clearance is neutrophil dependent and thus ‘self-regulated’. Pegfilgrastim is administered as a single subcutaneous injection per cycle of chemotherapy. In clinical trials it has been shown to be comparable in efficacy to filgrastim in decreasing the incidence of infection as manifested by febrile neutropenia following chemotherapy. Its safety profile and tolerability are similar to those of filgrastim.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Fig. 3
Fig. 4
Table II
Fig. 5
Table III
Table IV

Similar content being viewed by others

References

  1. Hughes WT, Armstrong D, Bodey GP, et al. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis 1997; 25: 551–73

    Article  CAS  Google Scholar 

  2. 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: 3558–85

    Article  CAS  Google Scholar 

  3. Wood W, Budman D, Korzun A, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 1994; 330: 1253–9

    Article  CAS  Google Scholar 

  4. Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 1995; 332: 901–6

    Article  CAS  Google Scholar 

  5. Budman DR, Berry DA, Cirrincione CT, 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

    Article  CAS  Google Scholar 

  6. Molineux G, Kinstler O, Briddell B, et al. A new form of filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 1999; 27: 1724–34

    Article  CAS  Google Scholar 

  7. Delgado C, Francis GE, Fisher D. The uses and properties of PEG-linked proteins. Crit Rev Ther Drug Carrier Syst 1992; 9: 249–304

    CAS  PubMed  Google Scholar 

  8. 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: 2522–8

    Article  CAS  Google Scholar 

  9. Price TH, Chatta GS, Dale DC. Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood 1996; 88: 335–40

    Article  CAS  Google Scholar 

  10. Weite K, Gabrilove J, Bronchud MH, et al. Filgrastim (r-metHuG-CSF): the first 10 years. Blood 1996; 88: 1907–29

    Article  Google Scholar 

  11. 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: 164–70

    Article  CAS  Google Scholar 

  12. 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: 319–24

    Article  Google Scholar 

  13. McKenna PJ, Korach E, Andresen J. Filgrastim SD, a sustained duration form of filgrastim (rhuG-CSF) has similar effects on neutrophil function compared to filgrastim [abstract #1562]. Blood 1998; 92(10) Suppl. (Pt 1): 379a

    Google Scholar 

  14. Allen RC, Mireles MA, Welch W, et al. Phase I study comparing daily filgrastim (SD/01) in normal volunteers: effects on neutrophil respiratory burst [abstract #3944]. Blood 1999; 94(10) Suppl. (Pt 2): 172b

    Google Scholar 

  15. Lord BI, WoolfordLB, Molineux G, et al. Kinetics of neutrophil production in normal and neutropenic animals during the response to filgrastim (r-metHu G-CSF) or filgrastim SD/01 (PEG-r-metHu G-CSF). Clin Cancer Res 2001; 7: 2085–90

    CAS  PubMed  Google Scholar 

  16. George S, Yunnus F, Yang B-B, et al. Pharmacokinetic profiles of fixed single dose pegfilgrastim administration in patients with non-Hodgkin’s lymphoma [abstract #3700]. Blood 2001; 98(11) Suppl. (Pt 2): 27b

    Google Scholar 

  17. Holmes FA, Jones SE, O’Shaughnessy JA, et al. A single dose of pegfilgrastim is as effective as daily filgrastim to reduce the duration of severe, chemotherapy-induced neutropenia [abstract #191]. Proceedings of the 36th Annual Meeting of the American Society of Clinical Oncology; 2000 May 20–23; New Orleans (LA)

  18. Holmes FA, O’Shaughnessy JA, Vukelja S, et al. 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 2002; 20: 727–31

    Article  CAS  Google Scholar 

  19. 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)

  20. Physician package insert. Neulasta™ (pegfilgrastim). Available from URL: http://www.fda.gov/cber/label/pegfamg01313102LB.pdf [Accessed 2002 Feb 22]

  21. Crawford J, Garst J, Lee M. A phase II multicycle trial of pegfilgrastim compared to filgrastim after myelosuppressive chemotherapy [abstract #922]. Presented at 9th World Conference, International Association for the Study of Lung Cancer; 2000 Sept 12; Tokyo

  22. Vose JM, Crump M, Lazarus H, et al. Single dose pegfilgrastim (SD/01) is as effective as daily filgrastim following ESHAP chemotherapy for subjects with non-Hodgkin’s lymphoma or Hodgkin’s disease: results of a randomized, open-label study [abstract #3322]. Blood 2001; 98(11) Suppl. (Pt 1): 799a

    Google Scholar 

  23. Yang B-B, Lum P, Renwick J, et al. Pharmacokinetic rationale for a fixed-dose regimen of a sustained-duration form of filgrastim in cancer patients [abstract #4384]. Blood 2000; 96(11) Suppl. (Pt 2): 157b

    Google Scholar 

  24. Data on file. Thousand Oaks (CA): Amgen Inc., Apr 2001; Study No.: 990749

  25. Hiddemann W, Grigg A, Solal-Celigny P. An open-label randomised, parallel, dose-ranging study of single administration SD/01 vs daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin’s [abstract #685]. Hematol J 2001; 1 Suppl. 1: 184

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Duke Medical Center, Room 25178 Morris Bldg., PO Box 3198, Durham, North Carolina, 27710-0001, USA

    Jeffrey Crawford

Authors
  1. Jeffrey Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey Crawford.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crawford, J. Pegfilgrastim Administered Once Per Cycle Reduces Incidence of Chemotherapy-Induced Neutropenia. Drugs 62 (Suppl 1), 89–98 (2002). https://doi.org/10.2165/00003495-200262001-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200262001-00007

Keywords

Search

Navigation