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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

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. 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. 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. 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. • Primary febrile neutropenia (FN) prophylaxis is indicated for docetaxel-cyclophosphamide (TC) chemotherapy. • In this multicentre trial 458 breast cancer patients receiving TC chemotherapy were randomised to ciprofloxacin or to G-CSF. • For the primary endpoint of FN and non-FN treatment-related hospitalizations, G-CSF was not superior over ciprofloxacin. • While there were reduced FN rates with G-CSF, the incremental cost-effectiveness ratio was C$1,760,796 per one QALYWALY gained. [ABSTRACT FROM AUTHOR]

Background: Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap. Methods: Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers. Results: Of 2105 identified records, 7 studies ( n = 2535) met the pre-specified eligibility criteria. Seven additional studies ( n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) ( n = 2256) and 11 retrospective studies ( n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim ( n = 1274), filgrastim ( n = 1758), and oral ciprofloxacin ( n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions. Conclusions: Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another. [ABSTRACT FROM AUTHOR]

Background Docetaxel–cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients. Patients and Methods This prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m 2 and C-600 mg/m 2 . Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT 3 ) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2. Results Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2–91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8–72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8–38.1, p = 0.0124) and 2 (18.3–42.9, p = 0.0059). Conclusions Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy. [ABSTRACT FROM AUTHOR]