A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia
Mark Clemons,
Dean Fergusson,
Anil A. Joy,
Kednapa Thavorn,
Judith Meza-Junco,
Julie Price Hiller,
John Mackey,
Terry Ng,
Xiaofu Zhu,
Mohammed F.K. Ibrahim,
Marta Sienkiewicz,
Deanna Saunders,
Lisa Vandermeer,
Gregory Pond,
Bassam Basulaiman,
Arif Awan,
Lacey Pitre,
Nancy A. Nixon,
Brian Hutton,
John F. Hilton
Affiliations
Mark Clemons
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; Corresponding author. Division of Medical Oncology Ottawa Hospital Research Institute, 501 Smyth Road, Box 912, Ottawa, Ontario, Canada.
Dean Fergusson
Clinical Epidemiology Program, Ottawa Hospital Research Institute and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
Anil A. Joy
Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada
Kednapa Thavorn
Clinical Epidemiology Program, Ottawa Hospital Research Institute and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
Judith Meza-Junco
Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada
Julie Price Hiller
Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada
John Mackey
Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada
Terry Ng
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
Xiaofu Zhu
Division of Medical Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada
Mohammed F.K. Ibrahim
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
Marta Sienkiewicz
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada
Deanna Saunders
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada
Lisa Vandermeer
Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada
Gregory Pond
Department of Oncology, McMaster University, Hamilton, Canada
Bassam Basulaiman
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
Arif Awan
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada
Lacey Pitre
Department of Oncology, Northeast Cancer Centre, Sudbury, Canada
Nancy A. Nixon
Division of Medical Oncology, Department of Oncology, University of Alberta, Tom Baker Cancer Centre, Calgary, Canada
Brian Hutton
Clinical Epidemiology Program, Ottawa Hospital Research Institute and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
John F. Hilton
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada
Background: Primary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. Methods: EBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. Results: 458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = −6.7%, 95%CI = −13.5%–0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p < 0.001). Non-FN treatment-related hospitalisation occurred in 40/228 (17.5%) of ciprofloxacin patients vs 28/230 (12.2%) of G-CSF patients (p = 0.12). There were no differences in other secondary outcomes. G-CSF was associated with an incremental cost-effectiveness ratio of C$1,760,796 per one quality-adjusted life year gained. Conclusion: The primary endpoint of superiority of G-CSF over ciprofloxacin was not demonstrated. While there were reduced FN rates with G-CSF, there were no differences in chemotherapy dose delays/reductions or discontinuations. With the commonly used willingness to pay value of C$50,000/QALY, G-CSF use was not cost-effective compared to ciprofloxacin and deserves scrutiny from the payer perspective.
