Skip to main content

Advertisement

SpringerLink
Log in

Comparison of pharmacokinetics and safety of pegfilgrastim administered by two delivery methods: on-body injector and manual injection with a prefilled syringe

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

For patients with clinically significant risk of febrile neutropenia, pegfilgrastim administration should occur the day after myelosuppressive chemotherapy; however, a variety of factors may preclude patients from returning to the clinic the next day for pegfilgrastim administration, necessitating other strategies. This study compared the pharmacokinetics and safety of pegfilgrastim administered via an on-body injector applied to the subject’s skin versus manual injection using a prefilled syringe.

Methods

Healthy subjects aged 18–50 years were randomized 1:1 to receive a single 6-mg subcutaneous pegfilgrastim dose from an on-body injector or a prefilled syringe. Blood for pharmacokinetic measurements was collected at baseline and prespecified time points after pegfilgrastim administration; safety was assessed throughout the 6-week study. Primary endpoints were maximum concentration (C max) and area under the concentration curve from time 0 to infinity (AUC0–inf). Secondary endpoints included safety, tolerability, and immunogenicity.

Results

Pegfilgrastim mean AUC0–inf values for the on-body injector (n = 125) and manual injection (n = 128) were 10,900 and 11,100 h ng/mL, respectively; mean C max values were 248 and 262 ng/mL, respectively. The least squares geometric mean ratios were 0.97 for C max and 1.00 for AUC0–inf; the corresponding 90 % CIs were within the prespecified range (0.80–1.25), indicating comparable pegfilgrastim pharmacokinetics between delivery methods. Treatment-emergent adverse events (AEs) were similar between groups (injector, 86 %; manual, 85 %). Injector- or syringe-related AEs were more prevalent with the injector (13 %; manual, 4 %); none were serious. No pegfilgrastim-neutralizing antibodies were detected.

Conclusions

Pegfilgrastim pharmacokinetics and safety were comparable between the on-body injector and manual injection groups.

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
Fig. 2

Similar content being viewed by others

References

  1. Leonard RC, Miles D, Thomas R, Nussey F, UK Breast Cancer Neutropenia Audit Group (2003) Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients. Br J Cancer 89:2062–2068

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Lyman GH, Dale DC, Friedberg J, Crawford J, Fisher RI (2004) Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 22:4302–4311

    Article  CAS  PubMed  Google Scholar 

  3. Lyman GH (2006) Chemotherapy dose intensity and quality cancer care. Oncology (Williston Park) 20:16–25

    Google Scholar 

  4. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258–2266

    Article  PubMed  Google Scholar 

  5. Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I, Kris M, Grous J, Picozzi V, Rausch G, Smith R, Gradishar W, Yahanda A, Vincent M, Stewart M, Glaspy J (1991) Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 325:164–170

    Article  CAS  PubMed  Google Scholar 

  6. Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, Neumann TA, Schwartzberg LS (2005) 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 23:1178–1184

    Article  CAS  PubMed  Google Scholar 

  7. Hecht JR, Pillai M, Gollard R, Heim W, Swan F, Patel R, Dreiling L, Mo M, Malik I (2010) 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. Clin Colorectal Cancer 9:95–101

    Article  CAS  PubMed  Google Scholar 

  8. Gisselbrecht C, Haioun C, Lepage E, Bastion Y, Tilly H, Bosly A, Dupriez B, Marit G, Herbrecht R, Deconinck E, Marolleau JP, Yver A, Dabouz-Harrouche F, Coiffier B, Reyes F, Groupe d’Etude des Lymphomes de l’Adulte (1997) Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin’s lymphoma: factors influencing chemotherapy administration. Leuk Lymphoma 25:289–300

    CAS  PubMed  Google Scholar 

  9. Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, Huang M, Crawford J (2013) 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 24:2475–2484

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205

    Article  CAS  PubMed  Google Scholar 

  11. National Comprehensive Cancer Network (2014) NCCN clinical practice guidelines in oncology: myeloid growth factors, version 2. www.NCCN.org. Accessed 2 Feb 2015

  12. Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C, European Organisation for Research and Treatment of Cancer (2011) 2010 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 47:8–32

    Article  CAS  PubMed  Google Scholar 

  13. Neulasta® (pegfilgrastim) (2015) Full prescribing information. Amgen Inc, Thousand Oaks

    Google Scholar 

  14. Meropol NJ, Miller LL, Korn EL, Braitman LE, MacDermott ML, Schuchter LM (1992) Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy. J Natl Cancer Inst 84:1201–1203

    Article  CAS  PubMed  Google Scholar 

  15. Crea F, Giovannetti E, Zinzani PL, Danesi R (2009) Pharmacologic rationale for early G-CSF prophylaxis in cancer patients and role of pharmacogenetics in treatment optimization. Crit Rev Oncol Hematol 72:21–44

    Article  PubMed  Google Scholar 

  16. Burris HA, Belani CP, Kaufman PA, Gordon AN, Schwartzberg LS, Paroly WS, Shahin S, Dreiling L, Saven A (2010) Pegfilgrastim on the same day versus next day of chemotherapy in patients with breast cancer, non–small-cell lung cancer, ovarian cancer, and non-Hodgkin’s lymphoma: results of four multicenter, double-blind, randomized phase II studies. J Oncol Pract 6:133–140

    Article  PubMed Central  PubMed  Google Scholar 

  17. Cheng C, Gallagher EM, Yeh JY, Earl MA (2014) Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab. Anticancer Drugs 25:964–969

    Article  CAS  PubMed  Google Scholar 

  18. Lokich JJ (2006) Same day pegfilgrastim and CHOP chemotherapy for non-Hodgkin lymphoma. Am J Clin Oncol 29:361–363

    Article  CAS  PubMed  Google Scholar 

  19. Schuman SI, Lambrou N, Robson K, Glück S, Myriounis N, Pearson JM, Lucci JA 3rd (2009) Pegfilgrastim dosing on same day as myelosuppressive chemotherapy for ovarian or primary peritoneal cancer. J Support Oncol 7:225–228

    CAS  PubMed  Google Scholar 

  20. Whitworth JM, Matthews KS, Shipman KA, Numnum TM, Kendrick JE, Kilgore LC, Straughn JM Jr (2009) The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in patients receiving myelosuppressive chemotherapy for gynecologic malignancies. Gynecol Oncol 112:601–604

    Article  CAS  PubMed  Google Scholar 

  21. Hoffman PS (2005) Administration of pegfilgrastim on the same day or next day of chemotherapy. J Clin Oncol 23:8137

    Google Scholar 

  22. Karol J, Rybicki L, Sweetenham J, Smith MR, Hill BT, Pohlman B, Jagadeesh D, Gazdick E, Fenner K, Maggiotto AL, Dean RM (2013) Similar incidence of febrile neutropenia with same-day versus subsequent day G-CSF administration in non-Hodgkin lymphoma patients receiving R-CHOP chemotherapy. Blood (ASH annual meeting) 122. Abstract 4357

  23. Weycker D, Wu H, Hagiwara M, Li X, Barron RL (2014) Use of chemotherapy and same-day pegfilgrastim prophylaxis in US clinical practice. Presented at: 56th annual meeting of the American Society of Hematology (ASH); San Francisco, CA

  24. Neulasta® (pegfilgrastim) Delivery Kit: healthcare provider instructions for use. http://pi.amgen.com/united_states/neulasta/neulasta_ifu_hcp_pt_english.pdf. Accessed 3 Feb 2015

  25. Yang BB, Kido A, Salfi M, Swan S, Sullivan JT (2008) Pharmacokinetics and pharmacodynamics of pegfilgrastim in subjects with various degrees of renal function. J Clin Pharmacol 48:1025–1031

    Article  CAS  PubMed  Google Scholar 

  26. Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P, Siena S, Lalisang RI, Samonigg H, Clemens MR, Zani V, Liang BC, Renwick J, Piccart MJ, the International Pegfilgrastim 749 Study Group (2003) A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 14:29–35

    Article  CAS  PubMed  Google Scholar 

  27. Holmes FA, O’Shaughnessy JA, Vukelja S, Jones SE, Shogan J, Savin M, Glaspy J, Moore M, Meza L, Wiznitzer I, Neumann TA, Hill LR, Liang BC (2002) 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 20:727–731

    Article  CAS  PubMed  Google Scholar 

  28. Yang BB, Kido A (2011) Pharmacokinetics and pharmacodynamics of pegfilgrastim. Clin Pharmacokinet 50:295–306

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This manuscript is dedicated to the memory of Dr. Michael Moxness who worked tirelessly in the pursuit of excellence in clinical immunology to enhance the drug discovery and development process. The authors acknowledge Ramak Pourvasei, BS (Amgen Inc.), and Marintan Spring, MS (Amgen Inc.), for their assistance with the PK sample and data analyses, respectively, as well as James Balwit, MS, whose work was funded by Amgen Inc., for assistance in writing this manuscript. This study was funded by Amgen Inc.

Conflict of interest

B-BY, PKM, and DP are employees of and stockholders in Amgen Inc. XW and MM were employees of and stockholders in Amgen Inc. at the time the study was conducted.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

  1. Amgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA

    Bing-Bing Yang, Phuong Khanh Morrow, Michael Moxness & Desmond Padhi

  2. Amgen Ltd, Uxbridge, UK

    Xikun Wu

Authors
  1. Bing-Bing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Phuong Khanh Morrow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xikun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Moxness
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Desmond Padhi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bing-Bing Yang.

Additional information

Michael Moxness—Deceased.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, BB., Morrow, P.K., Wu, X. et al. Comparison of pharmacokinetics and safety of pegfilgrastim administered by two delivery methods: on-body injector and manual injection with a prefilled syringe. Cancer Chemother Pharmacol 75, 1199–1206 (2015). https://doi.org/10.1007/s00280-015-2731-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-015-2731-x

Keywords

Search

Navigation