Advertisement

Supportive Care in Cancer

, Volume 19, Issue 11, pp 1789–1795 | Cite as

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)

  • Sibylle LoiblEmail author
  • Volkmar Mueller
  • Gunter von Minckwitz
  • Bettina Conrad
  • Claus-Henning Koehne
  • Stephan Kremers
  • Helmut Forstbauer
  • Mattea Linder
  • Valentina Nekljudova
  • Volker Moebus
  • On behalf of the GBG/AGO/NOGGO study groups
Original Article

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.

Keywords

Pegfilgrastim Neutropenia Primary breast cancer Dose-dense chemotherapy Leucopenia Febrile 

Notes

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.

Supplementary material

520_2010_1020_MOESM1_ESM.doc (142 kb)
ESM 1 (DOC 142 kb)

References

  1. 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 21:1431–1439CrossRefGoogle Scholar
  2. 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 27:2938–2945PubMedCrossRefGoogle Scholar
  3. 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 28:2874–2880CrossRefGoogle Scholar
  4. 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 45:608–617CrossRefGoogle Scholar
  5. 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 42:2433–2453PubMedCrossRefGoogle Scholar
  6. 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 74:203–210PubMedCrossRefGoogle Scholar
  7. 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 19:292–298CrossRefGoogle Scholar
  8. 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. 9.
    Renwick W, Pettengell R, Green M (2009) Use of filgrastim and pegfilgrastim to support delivery of chemotherapy: twenty years of clinical experience. BioDrugs 23:175–186PubMedCrossRefGoogle Scholar
  10. 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):19511Google Scholar
  11. 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 112:601–604PubMedCrossRefGoogle Scholar
  12. 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 77:107–112PubMedCrossRefGoogle Scholar
  13. 13.
    Amgen (2008) Neulasta® (pegfilgrastim) prescribing information. Amgen, Thousand OaksGoogle Scholar
  14. 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):1065Google Scholar
  15. 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 21:514–519PubMedCrossRefGoogle Scholar
  16. 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 14:29–35PubMedCrossRefGoogle Scholar
  17. 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. 568Google Scholar
  18. 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):568Google Scholar
  19. 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 18:2522–2528PubMedGoogle Scholar
  20. 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 20:727–731PubMedCrossRefGoogle Scholar
  21. 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 15:7361–7367PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sibylle Loibl
    • 1
    Email author
  • Volkmar Mueller
    • 2
  • Gunter von Minckwitz
    • 1
  • Bettina Conrad
    • 3
  • Claus-Henning Koehne
    • 4
  • Stephan Kremers
    • 5
  • Helmut Forstbauer
    • 6
  • Mattea Linder
    • 1
  • Valentina Nekljudova
    • 1
  • Volker Moebus
    • 7
  • On behalf of the GBG/AGO/NOGGO study groups
  1. 1.German Breast GroupNeu-IsenburgGermany
  2. 2.Universitätsklinikum Hamburg-EppendorfHamburgGermany
  3. 3.Elisabeth KrankenhausKasselGermany
  4. 4.Klinikum OldenburgOldenburgGermany
  5. 5.Caritas Krankenhaus LebachLebachGermany
  6. 6.GOSPL—Gesellschaft für onkologische Studien-Hämatologie und OnkologieTroisdorfGermany
  7. 7.Städtische Kliniken Frankfurt HöchstFrankfurt am MainGermany

Personalised recommendations