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 R. Mackey, Terry L. Ng, Xiaofu Zhu, Mohammed Ibrahim, Marta Sienkiewicz, Deanna Saunders, Lisa Vandermeer, Gregory R. Pond, Bassam Basulaiman, Arif Awan, Lacey D. Pitre, Nancy Nixon, Brian Hutton, John Hilton
Abstract
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.