Skip to main content

Advertisement

Log in

Comparison of pegfilgrastim on day 2 vs. day 4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study: (GBG 33)

Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Background

Preliminary data suggest that pegfilgrastim given on day 4 (P4) might be superior to pegfilgrastim on day 2 (P2) in reducing grade 4 leucopenia.

Methods

Patients with node-positive primary breast cancer receiving epirubicin–paclitaxel–cyclophosphamide chemotherapy were randomized to receive P2 versus P4. Primary endpoint was leucopenia grade 4, assuming a risk reduction of 50% with P4 from 50% in P2 to 25% with P4.

Results

Three-hundred fifty-one patients were randomized to P2 (n = 174) versus P4 (n = 177). The rate of leucopenia (grade 4) was 47.1% with P2 and 42.0% with P4 (p = 0.387), neutropenia (grade 3 + 4) was 47.9% versus 40.8% (p = 0.337), FN was 4.7% versus 8.0% (p = 0.271), and infections was 29.9% versus 25.4% (p = 0.404), respectively.

Conclusion

This study failed to demonstrate that pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Citron MLBerry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ et al (2003) 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 Oncol 21:1431–1439

    Article  Google Scholar 

  2. Untch M, Möbus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I et al (2009) Intensive dose-dense chemotherapy compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 27:2938–2945

    Article  PubMed  Google Scholar 

  3. Möbus V, Jackisch C, Lück HJ, du Bois A, Thomssen C, Kurbacher C et al (2010) Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer (4+ LN): mature results of an AGO-phase-III study. J Clin Oncol 28:2874–2880

    Article  Google Scholar 

  4. von Minckwitz G, Schwenkglenks M, Skacel T, Lyman GH, Pousa AL, Bacon P et al (2009) Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: results from an integrated analysis. Eur J Cancer 45:608–617

    Article  Google Scholar 

  5. Aapro MS, Cameron DA, Pettengell R, Bohlius J, Crawford J, Ellis M et al (2006) 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 Cancer 42:2433–2453

    Article  PubMed  CAS  Google Scholar 

  6. Aapro M, Schwenkglenks M, Lyman GH, Lopez Pousa A, Lawrinson S, Skacel T et al (2009) Pegfilgrastim primary prophylaxis vs. current practice neutropenia management in elderly breast cancer patients receiving chemotherapy. Crit Rev Oncol Hematol 74:203–210

    Article  PubMed  Google Scholar 

  7. von Minckwitz G, Kümmel S, du Bois A, Eiermann W, Eidtmann H, Gerber B et al (2008) Pegfilgrastim ± ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. Ann Oncol 19:292–298

    Article  Google Scholar 

  8. National Comprehensive Cancer Network (2010) Practice guidelines in oncology v.1.2010. Myeloid growth factors. Available at:http://www.nccn.org/professionals/physician_gls/PDF/myeloid_growth.pdf. Accessed 21 Apr 2010

  9. Renwick W, Pettengell R, Green M (2009) Use of filgrastim and pegfilgrastim to support delivery of chemotherapy: twenty years of clinical experience. BioDrugs 23:175–186

    Article  PubMed  CAS  Google Scholar 

  10. Hartmann F, Zeynalova S, Nickenig C, Reiser M, Lengfelder E, Duerk H et al (2007) Peg-filgrastim (Peg-F) on day 4 of (R-)CHOP-14 chemotherapy compared to day 2 in elderly patients with diffuse large B-cell lymphoma (DLBCL): results of a randomized trial of the German high-grade non-Hodgkin’s lymphoma study group (DSHNHL). J Clin Oncol 25(18S):19511

    Google Scholar 

  11. Whitworth JM, Matthews KS, Shipman KA, Numnum TM, Kendrick JE, Kilgore LC et al (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  PubMed  CAS  Google Scholar 

  12. Skarlos DV, Timotheadou E, Galani E, Samantas E, Grimani I, Lianos E et al (2009) Pegfilgrastim administered on the same day with dose-dense adjuvant chemotherapy for breast cancer is associated with a higher incidence of febrile neutropenia as compared to conventional growth factor support: matched case–control study of the Hellenic Cooperative Oncology Group. Oncology 77:107–112

    Article  PubMed  CAS  Google Scholar 

  13. Amgen (2008) Neulasta® (pegfilgrastim) prescribing information. Amgen, Thousand Oaks

    Google Scholar 

  14. Loibl S, Nekljudova N, Skacel T, Schwenkglenks M, Lück HJ, Brodowicz T, Zielinski C, von Minckwitz G (2009) Evaluating the impact of relative total dose intensity (RTDI) on patient’s short- and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer: a pooled analysis. J Clin Oncol 27(15S):1065

    Google Scholar 

  15. Vose JM, Crump M, Lazarus H, Emmanouilides C, Schenkein D, Moore J et al (2003) Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol 21:514–519

    Article  PubMed  CAS  Google Scholar 

  16. Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P et al (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  PubMed  CAS  Google Scholar 

  17. Saven A, Schwartzberg L, Kaywin P, Bartlett N, Dean L, Shahin S et al (2006) Randomized, double blind phase II study evaluated same-day vs. next-day administration of pegfilgrastim with R-CHOP in non-Hodgkin’s lymphoma patients. J Clin Oncol 24(suppl 18S):7570, abstr. 568

    Google Scholar 

  18. Möbus V, Conrad B, Schneeweiss A, Kreienberg R, Solomayer EF, Clemens MR et al (2009) Gain study: a phase III trial to compare ETC versus EC-TX and ibandronate versus observation in patients with node-positive primary breast cancer. J Clin Oncol 27(15S):568

    Google Scholar 

  19. Crawford J, Blackwell S, Bjurstrom T, Lockbaum P, Roskos L et al (2000) Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 18:2522–2528

    PubMed  Google Scholar 

  20. Holmes FA, O’Shaughnessy JA, Vukelja S, Jones SE, Shogan J, Savin M et al (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  PubMed  CAS  Google Scholar 

  21. Fox E, Widemann BC, Hawkins DS, Jayaprakash N, Dagher R, Aikin AA et al (2009) Randomized trial and pharmacokinetic study of pegfilgrastim versus filgrastim after dose-intensive chemotherapy in young adults and children with sarcomas. Clin Cancer Res 15:7361–7367

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank all the patients who participated in this study as well as all study personnel and investigators. Amgen Germany provided financial support for the whole GAIN trial.

Conflict of interest

The main study received financial and drug support from Amgen, Germany and Roche, Germany. The substudy did not receive additional funding. None of the authors has a potential conflict of interest.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Sibylle Loibl.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 142 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loibl, S., Mueller, V., von Minckwitz, G. et al. Comparison of pegfilgrastim on day 2 vs. day 4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study: (GBG 33). Support Care Cancer 19, 1789–1795 (2011). https://doi.org/10.1007/s00520-010-1020-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-010-1020-9

Keywords

Navigation