Semashko Clinical Hospital, #2, Moscow, Russia.
Expert Opin Drug Saf. 2010 Jul;9(4):515-23. doi: 10.1517/14740338.2010.487063.
This pilot open-label clinical study evaluated the safety and pharmacokinetics of albumin-bound paclitaxel (nab-paclitaxel) in patients with advanced solid tumors and hepatic dysfunction.
RESEARCH DESIGN/METHODS: Dosing was determined according to baseline bilirubin levels as described in the package insert for Taxol((R)) (paclitaxel), and patients received 130, 200 or 260 mg/m(2) nab-paclitaxel every 3 weeks.
Thirty patients with elevated baseline bilirubin and aspartate aminotransferase levels received nab-paclitaxel. The most commonly-occurring grade 3/4 adverse events were neutropenia and fatigue. Grade 3/4 neutropenia occurred in 10, 30 and 30% of patients receiving 130, 200 and 260 mg/m(2) nab-paclitaxel, respectively. Grade 3 fatigue presented in 50 and 30% patients receiving 130 and 200 mg/m(2) nab-paclitaxel, respectively (no grade 4 event). Only one (10%) patient had a grade 3 sensory neuropathy in the 260 mg/m(2) nab-paclitaxel arm. Treatment-related grade 3 bilirubinemia and elevated aspartate aminotransferase was observed in patients receiving 130 mg/m(2) (30 and 10%, respectively) and 260 mg/m(2) nab-paclitaxel (20 and 10%, respectively). One patient had a grade 4 bilirubinemia in the 200 mg/m(2) nab-paclitaxel arm. Total bilirubin levels were inversely correlated to paclitaxel clearance (p < 0001).
nab-Paclitaxel has an acceptable tolerability profile in patients with solid tumors and hepatic dysfunction. The safety and pharmacokinetic results support the same dose modification scheme recommended for cremophor-based paclitaxel.
本开放性临床试验初步评估了白蛋白结合型紫杉醇（nab-紫杉醇）在患有晚期实体瘤和肝功能障碍患者中的安全性和药代动力学。
研究设计/方法：根据 Taxol((R))（紫杉醇）说明书中的描述，根据基线胆红素水平确定剂量，患者每 3 周接受 130、200 或 260mg/m2nab-紫杉醇治疗。
30 例基线胆红素和天门冬氨酸转氨酶升高的患者接受了 nab-紫杉醇治疗。最常发生的 3/4 级不良事件是中性粒细胞减少和疲劳。分别有 10%、30%和 30%的患者接受 130、200 和 260mg/m2nab-紫杉醇治疗后出现 3/4 级中性粒细胞减少症。分别有 50%和 30%的患者接受 130 和 200mg/m2nab-紫杉醇治疗后出现 3 级疲劳（无 4 级事件）。在 260mg/m2nab-紫杉醇组中，仅有 1 例（10%）患者出现 3 级感觉神经病变。在接受 130mg/m2nab-紫杉醇治疗的患者中（分别为 30%和 10%）和接受 260mg/m2nab-紫杉醇治疗的患者中（分别为 20%和 10%）观察到与治疗相关的 3 级胆红素血症和天门冬氨酸转氨酶升高。在 200mg/m2nab-紫杉醇组中，有 1 例患者出现 4 级胆红素血症。总胆红素水平与紫杉醇清除率呈负相关（p < 0.0001）。
nab-紫杉醇在患有实体瘤和肝功能障碍的患者中具有可接受的耐受性。安全性和药代动力学结果支持与聚氧乙基代蓖麻油紫杉醇相同的剂量调整方案。
