Efficacy of pegfilgrastim to support neoadjuvant dose-dense epirubicin and cyclophosphamide chemotherapy in breast cancer
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The role of long-acting hematopoietic growth factor in supporting dose-dense chemotherapy and minimizing hematologic toxicity has not been established. We investigated the efficacy and safety of once-per-cycle pegfilgrastim in breast cancer patients receiving neoadjuvant dose-dense epirubicin and cyclophosphamide (ddEC).
Newly diagnosed stage I to III breast cancer patients received four cycles of ddEC (E, 100 mg/m2 and C, 600 mg/m2 every 2 weeks) and 6 mg of subcutaneous pegfilgrastim on day 2 of each cycle. The primary endpoint was to evaluate the incidence of chemotherapy delay. Secondary endpoints include the incidences of febrile neutropenia (FN) and grade 3/4 neutropenia during the four ddEC cycles.
A total of 240 patients were enrolled and 913 ddEC cycles were administered in the study. Chemotherapy delay occurred in 15 patients (6.3% of patients, 95% CI 3.2–9.4%) for 17 cycles (1.9% of cycles, 95% CI 1.0–2.8%). The most frequent cause of chemotherapy delay was transaminase elevation (10 patients, 12 cycles). A total of 12 patients (5.0%, 95% CI 2.2–7.8%) developed 13 episodes of FN. Of the 221 patients that completed four ddEC cycles with pegfilgrastim support, 209 patients (94.6%, 95% CI 91.6–97.6%) had a 100% relative dose intensity (RDI). A RDI ≥ 85% was achieved in 217 of 221 patients (98.2%, 95% CI 96.5–99.9%). Bone pain of any grade was recorded in 85 of 220 evaluable patients (38.6%, 95% CI 32.2–45.0%).
Pegfilgrastim is effective and safe in facilitating four cycles of neoadjuvant ddEC, with low incidences of chemotherapy delay and febrile neutropenia.
KeywordsPegfilgrastim Febrile neutropenia Dose-dense chemotherapy Breast cancer
This work was supported by CSPC Pharma by means of providing the pegfilgrastim used in the study. However, they were not involved in the collection, analysis, or interpretation of the data, nor in the decision to submit for publication. The corresponding author confirms that he had access to all data and had final responsibility for the decision to submit for publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Citron ML, Berry DA, Cirrincione C 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
- 5.Aapro MS, Bohlius J, Cameron DA, Lago LD, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulatingfactor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders andsolid tumours. Eur J Cancer 47:8–32CrossRefGoogle Scholar
- 6.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 ofrecommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205CrossRefGoogle Scholar
- 7.Holmes FA, Jones SE, O'Shaughnessy J, Vukelja S, George T, Savin M, Richards D, Glaspy J, Meza L, Cohen G, Dhami M, Budman DR, Hackett J, Brassard M, Yang BB, Liang BC (2002) Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 13:903–909CrossRefGoogle Scholar
- 8.Naeim A, Henk HJ, Becker L, Chia V, Badre S, Li X, Deeter R (2013) Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer 13:11CrossRefGoogle Scholar
- 9.Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP (2005) Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol 23:8340–8347CrossRefGoogle Scholar
- 10.Kourlaba G, Dimopoulos MA, Pectasides D, Skarlos DV, Gogas H, Pentheroudakis G, Koutras A, Fountzilas G, Maniadakis N (2015) Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer. Support Care Cancer 23:2045–2051CrossRefGoogle Scholar
- 14.Morita S, Kikumori T, Tsunoda N, Inaishi T, Adachi Y, Ota A, Shibata M, Matsuoka A, Nakanishi K, Takeuchi D, Mizutani T, Shimokata T, Hayashi H, Maeda O, Ando Y (2018) Feasibility of dose-dense epirubicin and cyclophosphamide with subcutaneous pegfilgrastim 3.6 mg support: a single-center prospective study in Japan. Int J Clin Oncol 23:195–200CrossRefGoogle Scholar
- 18.von Minckwitz G, Schwenkglenks M, Skacel T, Lyman GH, Pousa AL, Bacon P, Easton V, Aapro MS (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
- 19.Natoli C, Cianchetti E, Tinari N, Angelucci D, Grassadonia A, Zilli M, Ficorella C, Ricevuto E, Grossi S, de Tursi M, Carella C, Rispoli A, Iacobelli S (2007) A phase II study of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine and pegfilgrastim support as preoperative therapy for patients with stage II, III A breast cancer. Ann Oncol 18:1015–1020CrossRefGoogle Scholar
- 20.Jones RL, Walsh G, Ashley S, Chua S, Agarwal R, O'Brien M, Johnston S, Smith IE (2009) A randomised pilot phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer. Br J Cancer 100:305–310CrossRefGoogle Scholar
- 21.Loibl S, Mueller V, von Minckwitz G et al (2011) 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 19:1789–1795CrossRefGoogle Scholar
- 22.Skarlos DV, Timotheadou E, Galani 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 77:107–112CrossRefGoogle Scholar
- 23.Hendler D, Rizel S, Yerushalmi R, Neiman V, Bonilla L, Braunstein R, Sulkes A, Stemmer SM (2011) Different schedules of granulocyte growth factor support for patients with breast cancer receiving adjuvant dose-dense chemotherapy: a prospective nonrandomized study. Am J Clin Oncol 34:619–624CrossRefGoogle Scholar
- 24.Lambertini M, Bruzzi P, Poggio F, Pastorino S, Gardin G, Clavarezza M, Bighin C, Pronzato P, del Mastro L (2016) Pegfilgrastim administration after 24 or 72 or 96 h to allow dose-dense anthracycline- and taxane-based chemotherapy in breast cancer patients: a single-center experience within the GIM2 randomized phase III trial. Support Care Cancer 24:1285–1294CrossRefGoogle Scholar