Medical Oncology

, Volume 29, Issue 3, pp 1495–1501

Febrile neutropenia in adjuvant docetaxel and cyclophosphamide (TC) with prophylactic pegfilgrastim in breast cancer patients: a retrospective analysis

  • Nuttapong Ngamphaiboon
  • Tracey L. O’Connor
  • Pooja P. Advani
  • Ellis G. Levine
  • Ellen B. Kossoff
Original Paper


US Oncology Research Trial 9735 reported that TC improved overall survival when compared to doxorubicin and cyclophosphamide in early-stage breast cancer. Despite 61% grades 3–4 neutropenia in the TC arm, only 5% of patients developed febrile neutropenia (FN) without primary prophylactic GCSF (ppGCSF). TC has risen in popularity, particularly in older patients or in those where an anthracycline is contraindicated. Other studies examining the toxicity of TC without ppGCSF reported a higher incidence of FN between 23 and 46%. We reviewed our institutional experience with ppGCSF and the TC regimen. Women treated with adjuvant TC and pegfilgrastim at Roswell Park Cancer Institute were identified from the pharmacy database between 8/2006 and 11/2010. Patient characteristics and comorbidities were abstracted. Endpoints included incidence of FN, hematologic toxicities, relative dose intensity (RDI), and other acute complications. Docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 were given every 21 day/cycle for a planned four cycles. All patients received pegfilgrastim 6 mg on day 3. One hundred and eleven women with median age of 56 years (27–79) were identified. Twenty-two percent of patients were ≥65 at diagnosis. Eight patients developed FN (7%). Ninety-five patients (86%) were able to complete four cycles. Completion rate was significantly lower in patients with age ≥65 (71% vs. 90%; P = 0.02). Incidence of hospitalization, delay, RDI <85%, and dose reduction were not significantly different between the age groups. The overall incidence of FN was 7%. Older patients were significantly less likely to complete four cycles of TC as planned. ppGCSF should be strongly considered in breast cancer patients receiving adjuvant TC chemotherapy.


Docetaxel cyclophosphamide Febrile neutropenia Pegfilgrastim Prophylaxis Granulocyte colony-stimulating factor Breast cancer 


  1. 1.
    Jones S, Holmes FA, O’Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol. 2009;27(8):1177–83. doi:10.1200/JCO.2008.18.4028.PubMedCrossRefGoogle Scholar
  2. 2.
    Aapro M, Bernard-Marty C, Brain EG, Batist G, Erdkamp F, Krzemieniecki K, et al. Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. Ann Oncol. 2011;22(2):257–67. doi:10.1093/annonc/mdq609.PubMedCrossRefGoogle Scholar
  3. 3.
    Ngamphaiboon N, Edge SB, Groman A, Wilding GE, Ademuyiwa FO, Levine EG, Watroba N, O’Connor TL. Factors affecting delivery of planned chemotherapy for breast cancer in older women. In: The 33rd Annual San Antonio Breast Cancer Symposium. 2010;abstract#851603.Google Scholar
  4. 4.
    Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24(34):5381–7. doi:10.1200/JCO.2006.06.5391.PubMedCrossRefGoogle Scholar
  5. 5.
    Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34(6):730–51. doi:10.1086/339215.PubMedCrossRefGoogle Scholar
  6. 6.
    Chan A, Fu WH, Shih V, Coyuco JC, Tan SH, Ng R. Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy. Support Care Cancer. 2011;19(4):497–504. doi:10.1007/s00520-010-0843-8.PubMedCrossRefGoogle Scholar
  7. 7.
    Kotasek D. Febrile neutropenia rates during docetaxel and cyclophosphamide (TC) adjuvant therapy in early breast cancer (EBC). J Clin Oncol 2011;29(suppl; abstr 1101).Google Scholar
  8. 8.
    Soni A, Brufsky A, Jankowitz RC, Rastogi P, Vogel VG, Puhalla S Incidence of febrile neutropenia with docetaxel plus cyclophosphamide in a university-based breast oncology clinic. J Clin Oncol. 2011;29(suppl; abstr 9061).Google Scholar
  9. 9.
    Vandenberg T, Younus J, Al-Khayyat S. Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice-a retrospective analysis. Curr Oncol. 2010;17(2):2–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Takabatake D, Taira N, Hara F, Sien T, Kiyoto S, Takashima S, et al. Feasibility study of docetaxel with cyclophosphamide as adjuvant chemotherapy for Japanese breast cancer patients. Jpn J Clin Oncol. 2009;39(8):478–83. doi:10.1093/jjco/hyp050.PubMedCrossRefGoogle Scholar
  11. 11.
    Myers R, Higgins B, Jeffrey M, Mova L, Rajagopal S, Jones G, Stakiw J. Chemotherapy induced febrile neutropenia of docetaxel with cyclophosphamide (TC) for adjuvant therapy of breast cancer in the community-reality check. In: The 32nd Annual San Antonio Breast Cancer Symposium. 2009;Abstract#2092.Google Scholar
  12. 12.
    NCCN. NCCN Guideline V1.2011 Myeloid Growth Factors. http://wwwnccnorg/professionals/physician_gls/pdf/myeloid_growthpdf (2011).
  13. 13.
    Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, et al. 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. 2011;47(1):8–32. doi:10.1016/j.ejca.2010.10.013.PubMedCrossRefGoogle Scholar
  14. 14.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRefGoogle Scholar
  15. 15.
    Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol. 1984;2(11):1281–8.PubMedGoogle Scholar
  16. 16.
    Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, et al. 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. 2005;23(6):1178–84. doi:10.1200/JCO.2005.09.102.PubMedCrossRefGoogle Scholar
  17. 17.
    NCI. Common Terminology Criteria for Adverse Events (CTCAE V.4). http://evsncinihgov/ftp1/CTCAE/CTCAE_403_2010-06-14_QuickReference_85x11pdf (2009).
  18. 18.
    Wildiers H, Reiser M. Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol. 2011;77(3):221–40. doi:S1040-8428(10)00032-6.PubMedCrossRefGoogle Scholar
  19. 19.
    Shayne M, Culakova E, Wolff D, Poniewierski MS, Dale DC, Crawford J, et al. Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy. Cancer. 2009;115(22):5319–28. doi:10.1002/cncr.24560.PubMedCrossRefGoogle Scholar
  20. 20.
    Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265–74. doi:10.1200/JCO.2005.04.173.PubMedCrossRefGoogle Scholar
  21. 21.
    Kuderer NM, Dale DC, Crawford J, Lyman GH. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. 2007;25(21):3158–67. doi:10.1200/JCO.2006.08.8823.PubMedCrossRefGoogle Scholar
  22. 22.
    Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J. Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med. 2007;147(6):400–11.PubMedGoogle Scholar
  23. 23.
    Bohlius J, Herbst C, Reiser M, Schwarzer G, Engert A. Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev. 2008;4:CD003189. doi:10.1002/14651858.CD003189.PubMedGoogle Scholar
  24. 24.
    Lyman GH, Kuderer NM, Djulbegovic B. Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy: a meta-analysis. Am J Med. 2002;112(5):406–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Lathia N, Mittmann N, DeAngelis C, Knowles S, Cheung M, Piliotis E, et al. Evaluation of direct medical costs of hospitalization for febrile neutropenia. Cancer. 2010;116(3):742–8. doi:10.1002/cncr.24773.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Nuttapong Ngamphaiboon
    • 1
  • Tracey L. O’Connor
    • 1
  • Pooja P. Advani
    • 2
  • Ellis G. Levine
    • 1
  • Ellen B. Kossoff
    • 3
  1. 1.Department of MedicineRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of Internal MedicineState University of New York at BuffaloBuffaloUSA
  3. 3.Department of PharmacyRoswell Park Cancer InstituteBuffaloUSA

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