The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis

Abstract

The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with the TC regimen, its dependence on patients' age, and the efficacy of G-CSFpp in reducing it in ESBC patients. We systematically searched the literature via PUBMED using the following terms: 'docetaxel', 'cyclophosphamide', 'febrile neutropenia', and 'breast cancer'. Inclusion criteria were full text peer-reviewed clinical studies in English reporting FN rates with TC regimen in relationship to G-CSFpp. Comprehensive meta-analysis software was used for all statistical analyses. Eight studies (N = 1542 patients) were included in our meta-analysis. The pooled mean FN rate was 23.2 % (95 % confidence interval (CI) 6.9-55.2 %; Q = 218.17, I (2) = 97.7). The FN risk in <65 years old patients was lower by 67.7 % compared to that in patients ≥65 years old (pooled odds ratio (OR) 0.323; 95 % CI 0.127-0.820; P = 0.017). The FN risk was reduced by 92.3 % with G-CSFpp (pooled OR 0.077; 95 % CI 0.013-0.460; P = 0.005). Our meta-analysis demonstrated that TC regimen was associated with ≥20 % FN risk, which was significantly higher in patients ≥65 years old and improved with G-CSFpp. G-CSFpp should be considered for all ESBC patients receiving TC regimen, especially those ≥65 years old.

Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma

“…Results from the analyses based on an alternative data source for the disutility of FN and with discount rates ranging from 0 to 3% were similar to the base case. Using an alternative data source for the probability of FN for the TC regimen [47] resulted in an increase in the ICER for PP with pegfilgrastim (vs. SP with pegfilgrastim) from €15,500 to €24,100 per QALY.

Fig. 2Deterministic and probabilistic sensitivity analyses.

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“…For DSAs, key model parameters were varied using 95% confidence intervals (CIs), standard errors, and plausible ranges derived from published literature (Tables 1, 2) to assess how univariate changes in key model parameters and parameter uncertainty impacted cost-effectiveness results. In addition to the DSAs, a scenario analysis was performed using an alternative data source for the baseline risk of FN (23.2%) [47]. …”

Model-based prediction of myelosuppression and recovery based on frequent neutrophil monitoring

“…Docetaxel is a commonly used anti-cancer agent [ 5 – 7 ] that possess pronounced myelosuppressive properties [ 8 ], which exposes the patient to a high risk for severe neutropenia and consequently life-threatening conditions such as febrile neutropenia (FN). Docetaxel, typically administered as a 1 h infusion every 3 weeks in multiple cycles depending on the cancer type, can cause high rates (>20%) of FN [ 9 ]. Prior to each administration of cytotoxic drugs, the absolute neutrophil count (ANC) is measured to confirm adequate levels, i.e.…”

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco

“…Granulocyte colony-stimulating factors (G-CSF) have been introduced to clinical practice to prevent or to treat neutropenia. G-CSF has proven to be highly effective in decreasing the number of FN incidents and neutropeniarelated infections as well as in shortening the duration of neutropenia [5]. As a result, antibiotics usage is decreased and sub-optimal dosing of chemotherapy is avoided.…”

“…As a result, antibiotics usage is decreased and sub-optimal dosing of chemotherapy is avoided. G-CSF is now highly recommended, as it significantly reduces the early mortality rate [5]. G-CSF administration is currently strongly advised when patients receive chemotherapy associated with high (estimated as greater than 20%) risk of FN.…”