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)
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.
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