Albumin‐bilirubin score for predicting neuropsychiatric symptoms in patients receiving ifosfamide‐based chemotherapy

Abstract

What is known and objective: Ifosfamide, an alkylating agent, is widely used in the treatment of malignant diseases. However, these treatments are often limited due to the incidence of neuropsychiatric symptoms such as delirium, seizures, hallucinations and agitation. In this study, we examined risk factors for neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy. Methods:The study cases were patients with cancer receiving ifosfamide-based chemotherapy between April 2007 and March 2018. Risk analysis for ifosfamiderelated neuropsychiatric symptoms was determined by time-dependent Cox proportional hazard regression analysis.Results and discussion: Of 183 eligible patients, 32 patients (17.5%) experienced ifosfamide-related neuropsychiatric symptoms. Time-dependent Cox proportional hazard model showed that the albumin-bilirubin (ALBI) score was significantly correlated with the incidence of ifosfamide-related neuropsychiatric symptoms (hazard ratio [HR] =1.45, 95% confidence interval [CI] = 1.05-2.01, p = 0.025). Additionally, there were correlations between the predicted risk of neuropsychiatric symptoms and ifosfamide-dose per cycle (HR =0.51, 95% CI = 0.27-0.94, p = 0.030) and creatinine clearance (Ccr) (HR = 0.53, 95% CI = 0.28-1.00, p = 0.050). In contrast, neither serum albumin nor total bilirubin was a significant risk factor for neuropsychiatric symptoms. What is new and conclusion:These findings indicate that ALBI score may be a useful biomarker for predicting neuropsychiatric symptoms in patients receiving ifosfamidebased chemotherapy.

The ALBI score: From liver function in patients with HCC to a general measure of liver function

“… 98 Several pharmacokinetic studies have assessed the role of liver dysfunction in relation to drug-induced adverse events. [99] , [100] , [101] …”

“… Liver function by ALBI and pharmacokinetics Shimizu et al. 99 Retrospective 183 Serum drug concentrations ALBI score could be used to assess variations in the serum concentration of methadone. Kokubun et al.…”

“…Other studies have reported the effect of liver function, as assessed by ALBI, on serum levels of tumor markers such as, CA-125 [97] and the frequency of muscle cramps in cirrhotic patients [98]. Several pharmacokinetic studies have assessed the role of liver dysfunction in relation to drug-induced adversity [99][100][101].…”

“…Although ALBI is widely used according to grade, the score on which 'grade' is based is, in fact, a continuous variable and, as such, is particularly appropriate for assessment of changes in liver function over time. Thus, changes in ALBI score have been reported during the progression of liver disease to cirrhosis and to decompensation [99,100], during the course of systemic therapy for HCC, and in response to viral suppression by antiviral therapy or other therapies for liver diseases. In patients with HCC who had undergone systemic therapy, the adverse effect of molecular-targeted drugs or immune-checkpoint inhibitors on liver function were often evaluated with the changes in ALBI score [102][103][104][105][106][107].…”