Efficacy and safety of dose-dense chemotherapy for early-stage breast cancer under prophylactic pegfilgrastim administration: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022

Background: In early-stage breast cancer, dose-dense chemotherapy, which involves the administration of standard doses at shorter intervals, is safer when administered with granulocyte colony-stimulating factor (G-CSF) to mitigate chemotherapy-induced neutropenia. This study aimed to thoroughly evaluate the advantages and disadvantages of dose-dense regimens based on the use of G-CSF. Methods: A systematic review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing dose-dense chemotherapy with prophylactic pegfilgrastim administration in early-stage breast cancer were included. Outcomes included overall survival, event-free survival, incidence of febrile neutropenia, quality of life (QOL), and pain. Meta-analyses were performed on outcomes with sufficient data. Results: Our literature search identified 23 RCTs. Overall survival and event-free survival showed a trend favoring dose-dense therapy (hazard ratio, 0.90, 0.90; 95% confidence interval [CI] 0.78 − 1.03, 0.80 − 1.01; p = 0.13; 0.07, respectively). The incidence of febrile neutropenia was similar between the groups (odds ratio, 0.90; 95% CI 0.58 − 1.40; p = 0.65). Mortality due to infection could not be compared owing to the small number of events. Pain increased with dose-dense therapy (odds ratio 2.57; 95% CI 1.00 − 6.62; p = 0.05), likely from G-CSF-induced bone pain. Only one study examined QOL, showing a decline with chemotherapy that recovered after treatment. Conclusions: Dose-dense chemotherapy trended toward improved survival outcomes without increasing the risk of infection, although pain increased. Further research should identify the specific subgroups that most benefit from dose-dense regimens. More data are needed on the impact on QOL.