Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC)
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Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin or granulocyte-colony stimulating factors [G-CSF]) for patients receiving docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the feasibility of using a novel pragmatic comparative effectiveness trial to compare these standard-of-care options.
Early-stage breast cancer patients receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial methodology consists of broad eligibility criteria, simply-defined endpoints, integrated consent model incorporating oral consent, and web-based randomisation in the clinic. Primary feasibility endpoints included patient and physician engagement (if > 50% of patients approached agree to participate and if > 50% of physicians approached patients for the study). Secondary clinical endpoints included the following: first occurrence rates of FN, treatment-related hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as patient satisfaction with the oral consent process.
Of 204 patients approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%) participating medical oncologists randomised patients. Median patient age was 57.7 (range 31.8–84.1). The 186 patients received 557 cycles of chemotherapy. Overall incidences of first events by patient (n = 186) were as follows: FN (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%), chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186, 19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of patients and 12.39% (69/557) of chemotherapy cycles had at least one of these first events. Patients were highly satisfied with the oral consent process.
This study met its feasibility endpoints. This model offers a means of comparing standard-of-care treatments in a practical and cost-efficient manner.
Trial registration: ClinicalTrials.gov: NCT02173262
KeywordsIntegrated consent model Breast cancer Febrile neutropenia Filgrastim Ciprofloxacin
We are grateful for patients and their families for their assistance with this study, as well as physicians for approaching patients. Highest accrual by physician was as follows: Clemons (95), Hilton (27), Joy (11), Tonkin (10), Price-Hiller (8), Zhu (6), and Verma (5).
Funding for this study was from the Department of Medicine’s Patient Quality and Safety Committee PQ&I Project Grant and matched funding from the Division of Medical Oncology.
Compliance with ethical standards
Conflict of interest
BH consults for Cornerstore Research. All other authors have nothing to disclose.
Research involving human participants
The study was approved by the local Research Ethics Board at each participating centre (The Ottawa Health Science Network Research Ethics Board and Health Research Ethics Board of Alberta).
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional 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.Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387. https://doi.org/10.1200/JCO.2006.06.5391 CrossRefPubMedGoogle Scholar
- 2.Younis T, Rayson D, Thompson K (2012) Primary G-CSF prophylaxis for adjuvant TC or FEC-D chemotherapy outside of clinical trial settings: a systematic review and meta-analysis. Support Care Cancer: official journal of the Multinational Association of Supportive Care in Cancer 20(10):2523–2530. https://doi.org/10.1007/s00520-011-1375-6 CrossRefGoogle Scholar
- 3.Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO, American Society of Clinical O (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33(28):3199–3212. https://doi.org/10.1200/JCO.2015.62.3488 CrossRefPubMedGoogle Scholar
- 4.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 R, Treatment of C (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(1):8–32. https://doi.org/10.1016/j.ejca.2010.10.013 CrossRefPubMedGoogle Scholar
- 6.Fernandes R, Mazzarello S, Stober C, Vandermeer L, Dudani S, Ibrahim MF, Majeed H, Perdrizet K, Shorr R, Hutton B, Fergusson D, Clemons M (2017) Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review. Breast Cancer Res Treat 161(1):1–10. https://doi.org/10.1007/s10549-016-4028-0 CrossRefPubMedGoogle Scholar
- 7.Hilton J, Vandermeer L, Sienkiewicz M, Mazzarello S, Hutton B, Stober C, Fergusson D, Blanchette P, Joy AA, Brianne Bota A, Clemons M (2018) Filgrastim use in patients receiving chemotherapy for early-stage breast cancer-a survey of physicians and patients. Support Care Cancer : official journal of the Multinational Association of Supportive Care in Cancer 26:2323–2331. https://doi.org/10.1007/s00520-018-4074-8 CrossRefGoogle Scholar
- 9.Ibrahim MFK, Hilton J, Mazzarello S, Fergusson D, Hutton B, Robinson A, Califaretti N, Hsu T, Gertler S, Mates M, Stober C, Vandermeer L, Mallick R, Clemons M (2017) A multi-center pragmatic, randomized, feasibility trial comparing standard of care schedules of filgrastim administration for primary febrile neutropenia prophylaxis in early-stage breast cancer. Breast Cancer Res Treat 168:371–379. https://doi.org/10.1007/s10549-017-4604-y CrossRefPubMedGoogle Scholar
- 13.de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, Roila F, Group EGW (2010) Management of febrile neutropenia: ESMO clinical practice guidelines. Ann Oncol : official journal of the European Society for Medical Oncology 21(Suppl 5):v252–v256. https://doi.org/10.1093/annonc/mdq196 CrossRefGoogle Scholar
- 14.Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA (2009) 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 27(8):1177–1183. https://doi.org/10.1200/JCO.2008.18.4028 CrossRefPubMedGoogle Scholar
- 15.Cancer Care Ontario GCSF Recommendations 2016. (2016). https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=352101
- 16.Fraser J, Steele N, Al Zaman A, Yule A (2011) Are patients in clinical trials representative of the general population? Dose intensity and toxicities associated with FE100C-D chemotherapy in a non-trial population of node positive breast cancer patients compared with PACS-01 trial group. Eur J Cancer 47(2):215–220. https://doi.org/10.1016/j.ejca.2010.10.001 CrossRefPubMedGoogle Scholar
- 18.Vandenberg T, Younus J, Al-Khayyat S (2010) 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 17(2):2–3CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Weycker D, Barron R, Edelsberg J, Kartashov A, Legg J, Glass AG (2014) Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis. BMC Health Serv Res 14:189. https://doi.org/10.1186/1472-6963-14-189 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Arnaout A, Kuchuk I, Bouganim N, Pond G, Verma S, Segal R, Dent S, Gertler S, Song X, Kanji F, Clemons M (2016) Can the referring surgeon enhance accrual of breast cancer patients to medical and radiation oncology trials? The ENHANCE study. Curr Oncol 23(3):e276–e279. https://doi.org/10.3747/co.23.2394 CrossRefPubMedPubMedCentralGoogle Scholar