Prediction of cabazitaxel-induced severe neutropenia based on dose-to-albumin ratio and evaluation of clinical utility.

Cabazitaxel is a highly protein-bound drug that has been associated with the development of severe neutropenia, and decreased albumin (Alb) levels may contribute to this phenomenon. For some highly protein-bound drugs, adjustment of drug concentration according to Alb levels is performed in clinical practice. On the other hand, in the case of cabazitaxel, a decrease in Alb levels may lead to an increased proportion of unbound drug at the same dose, which could potentially raise the risk of developing severe neutropenia. Therefore, in this study, we investigated the usefulness of a novel index, the cabazitaxel dose divided by the Alb level (Dose/Alb), as a more accurate predictor of severe neutropenia in patients with metastatic castration-resistant prostate cancer receiving cabazitaxel. Thirty-nine patients were divided into two groups: 14 patients with grade 3-4 neutropenia and 25 with grade 0-2 neutropenia. Dose/Alb at the initiation of cabazitaxel was significantly higher in the grade 3-4 neutropenia group than in the grade 0-2 group (<i>P</i> = 0.013). Logistic regression analysis revealed that Dose/Alb was associated with the development of grade 3-4 neutropenia (odds ratio = 1.70, <i>P</i> = 0.021). Receiver operating characteristic analysis identified a cutoff value of 10.5 mg/g/dL; 75.0% of patients with Dose/Alb > 10.5 mg/g/dL developed grade 3-4 neutropenia, versus 18.5% with Dose/Alb ≤ 10.5 mg/g/dL (<i>P</i> < 0.01). The present study shows that a Dose/Alb-based prediction method may be able to predict the risk of developing grade 3-4 neutropenia at the time of the first dose of cabazitaxel.