The incidence of
neutropenia in metastatic
castration-resistant
prostate cancer (mCRPC) patients treated with
docetaxel has been reported to be lower compared to patients with other solid
tumors treated with a similar dose. It is suggested that this is due to increased clearance of
docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid
tumors by conducting a meta-analysis, (2) evaluate the incidence of
neutropenia in patients with mCRPC vs other solid
tumors in a clinical cohort, and (3) discuss potential clinical consequences. A meta-analysis was conducted of studies which reported areas under the plasma concentration-time curves (AUCs) of
docetaxel and variability. In addition, grade 3/4
neutropenia was evaluated using logistic regression in a cohort of patients treated with
docetaxel. The meta-analysis included 36 cohorts from 26 trials (n = 1150 patients), and showed that patients with mCRPC had a significantly lower mean AUC vs patients with other solid
tumors (fold change [95% confidence interval (CI)]: 1.8 [1.5-2.2]), with corresponding AUCs of 1.82 and 3.30 mg∙h/L, respectively. Logistic regression, including 812 patient, demonstrated that patients with mCRPC had a 2.2-fold lower odds of developing grade 3/4
neutropenia compared to patients with other solid
tumors (odds ratio [95%CI]: 0.46 [0.31-0.90]). These findings indicate that mCRPC patients have a lower risk of experiencing severe
neutropenia, possibly attributable to lower systemic exposure to
docetaxel.