Medical School, National and Kapodistrian University of Athens, Evgenidion Hospital, Greece.
Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
J Vasc Interv Radiol. 2022 Jul;33(7):752-761. doi: 10.1016/j.jvir.2021.11.019. Epub 2022 Mar 26.
Polyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC).
The current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0. Patients in Cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed on the basis of the specific dose of doxorubicin that the patients received because some patients received less than the assigned dose. Patients in Cohort II received the maximum safe tested dose. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 4.03. The tumor response was evaluated every 3 months according to the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors.
The maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75-100, and 101-150 mg of doxorubicin, the peak plasma concentrations were 286.7 ng/mL ± 220.1, 157.1 ng/mL ± 94.6, and 245.4 ng/mL ± 142.8, respectively; the areas under the curves calculated from 0 to 24 h were 421.7 (ng × h)/mL ± 221.2, 288.1 (ng × h)/mL ± 100.9, and 608.3 (ng × h)/mL ± 319.3, respectively, with almost complete clearance at 24 h. There was no death within 30 d. The best objective response rate was 81%, and the disease control rate was 91%. The median overall survival was 27.2 months (95% confidence interval [CI], 17.5 months to not evaluated [n.e.]); the median progression-free survival was 9.8 months (95% CI, 5.5 months to n.e.).
PEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.
聚乙二醇载药微球（PEG-DEMs）可加载阿霉素进行洗脱。本研究评估了 PEG-DEMs 在治疗肝细胞癌（HCC）患者中的药代动力学特征和安全性。
本前瞻性、多中心、剂量递增研究纳入了 25 例（68%为男性）早期或中期 HCC 且体能状态为 0 分的患者。队列 I 中的患者被分配接受目标阿霉素剂量 75、100 或 150mg。由于部分患者接受的剂量低于分配剂量，因此根据患者接受的具体阿霉素剂量进行了分析。队列 II 中的患者接受了最大安全测试剂量。根据通用不良事件术语标准 4.03 对不良事件进行分类。根据欧洲肝脏研究协会标准和实体瘤反应评价标准修订版，每 3 个月评估肿瘤反应。
阿霉素的最大测试安全剂量为 150mg。对于接受≤75mg、75-100mg 和 101-150mg 阿霉素的组，峰血浆浓度分别为 286.7ng/mL±220.1、157.1ng/mL±94.6 和 245.4ng/mL±142.8；0 至 24 小时的曲线下面积分别为 421.7（ng×h）/mL±221.2、288.1（ng×h）/mL±100.9 和 608.3（ng×h）/mL±319.3，24 小时几乎完全清除。30 天内无死亡。最佳客观缓解率为 81%，疾病控制率为 91%。中位总生存期为 27.2 个月（95%置信区间 [CI]：17.5 个月至未评估[n.e.]）；中位无进展生存期为 9.8 个月（95%CI：5.5 个月至 n.e.）。
PEG-DEMs 表现出良好的安全性，阿霉素全身浓度低，疗效有潜力。
