This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function,n= 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment,n= 8), or <30 mL/min (Cohort 3, severe renal impairment,n= 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment.
这项开放性I期研究（临床试验注册号：NCT03555955）评估了CPX-351在肾功能正常或受损的血液恶性肿瘤患者中的药代动力学（PK）及安全性。根据肌酐清除率（CrCl）将患者分为三个队列：≥90 mL/min（队列1，肾功能正常，n=7）、30至<59 mL/min（队列2，中度肾功能不全，n=8）或<30 mL/min（队列3，重度肾功能不全，n=6）。患者接受静脉注射CPX-351进行初始诱导治疗；收集血液和尿液样本进行PK分析。主要研究目的是评估阿糖胞苷、柔红霉素及其相应代谢产物阿糖尿苷（Ara-U）和柔红霉素醇的PK参数。肾功能损害未显著影响阿糖胞苷、柔红霉素或柔红霉素醇的暴露量，但导致Ara-U暴露量轻微增加。与肾功能正常患者相比，肾功能不全患者的CPX-351不良反应特征相似。所有患者均报告了≥1项治疗期间出现的不良事件（TEAE），最常见的是发热性中性粒细胞减少症和恶心（各57%）以及高血糖（43%）；无患者因TEAEs终止治疗。这些数据表明，对于中重度肾功能不全的血液恶性肿瘤患者，无需调整CPX-351剂量。
肿瘤(癌症)患者之家