Effect of renal function on neutrophil decreases following eribulin administration

Abstract

Background: Eribulin therapy has recently attracted attention from various viewpoints, including quality of life, and is considered a standard therapy for inoperable or recurrent breast cancer. Although a reduction in renal function reportedly decreases total eribulin clearance, its association with dose-limiting toxicity and the reduction of neutrophils remain unclear. Aim: This study was aimed at analyzing the association between decreased renal function prior to eribulin administration and the occurrence of neutrophil reduction and time to treatment failure in patients with breast cancer. Methods and Results: We retrospectively assessed patients with breast cancer, who underwent eribulin therapy between July 2011 and March 2018. Multivariate analysis revealed creatinine clearance <70 mL/min and serum albumin levels <3.9 mg/dL as predictive factors for neutrophil reduction. Even on increasing the relative dose intensity by these factors, no difference in time to treatment failure was observed, suggesting that treatment efficacy is potentially unaffected. Conclusions: For continuous eribulin therapy, eribulin may need to be administered to individual patients in accordance with renal function and albumin levels before treatment initiation.

Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer

“…In their logistic analysis, the authors used at baseline (<2,900), which had a decisive influence on the results. A previous study reported that a baseline neutrophil count of <3,000 was a risk factor for severe neutropenia, which supports our results (10,12). High AST and bilirubin levels are risk factors for liver dysfunction.…”

“…Therefore, we considered it theoretically consistent that high AST and bilirubin levels were identified as risk factors in this study. Furthermore, creatinine clearance <50 ml/min alone was not identified as a risk factor for severe neutropenia in this study, although it has been reported as a risk factor for severe neutropenia in prior renal function-adjusted studies (12). However, in an additional validation of this study, the frequency of severe neutropenia was 80% when the drug was used at 100% without a dose reduction in creatinine clearance of <50 ml/min; whereas the incidence decreased to 17% when the dose was reduced.…”

“…Multivariate analyses were performed using logistic regression to identify the independent risk factors associated with severe neutropenia. The following covariates were used in the analyses: age, neutropenia (10)(11)(12), aspartate aminotransferase (AST) (7), alanine aminotransferase (ALT) (7), total bilirubin (7), hemoglobin (13,14), platelets (15,16), and body mass index (BMI) (13,17,18). The evaluated pretreatment covariates were established based on previous reports on availability, prior evidence, and biological validity.…”