A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer.
A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer.
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DOI：
10.1038/bjc.2013.408
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发表时间：
2013-08-20
影响因子：
8.8
通讯作者：
Chen LT
中科院分区：
文献类型：
--
作者：
Ko AH;Tempero MA;Shan YS;Su WC;Lin YL;Dito E;Ong A;Wang YW;Yeh CG;Chen LT
PEP02，也称为MM-398，是一种新型纳米脂质体伊立替康，改善了游离药物的药代动力学和肿瘤生物分布。这项 2 期研究评估了 PEP02 单药疗法作为胰腺癌二线治疗的效果。患有转移性胰腺癌、卡诺夫斯基体能状态⩾70、并且在基于吉西他滨的治疗后病情进展的患者符合资格。每3周静脉注射PEP02 120mgm−2。采用西蒙2级设计。主要目标是 3 个月生存率 (OS3-month)。共有 40 名患者入组。最常见的严重不良事件包括中性粒细胞减少、腹痛、乏力和腹泻。 3 名患者 (7.5%) 获得了客观缓解，另外 17 名患者 (42.5%) 在至少两个周期内表现出疾病稳定。 32 名基线 CA19-9 升高的患者中，有 10 名 (31.3%) 的生物标志物下降 >50%。该研究达到了主要终点，3 个月 OS 为 75%，中位无进展生存期和总生存期分别为 2.4 个月和 5.2 个月。 PEP02 对转移性吉西他滨难治性胰腺癌患者具有中等抗肿瘤活性，且副作用可控。鉴于该患者群体可用的治疗选择有限，PEP02 (MM-398)（称为 NAPOLI-1）的 3 期试验目前正在进行中。
PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer. Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ⩾70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m−2 was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS3-month). A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS3-month of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively. PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.
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影响因子：
3
作者：
Ko, Andrew H.;Venook, Alan P.;Tempero, Margaret A.
通讯作者：
Tempero, Margaret A.
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3
作者：
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影响因子：
8.8
作者：
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影响因子：
5.8
作者：
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通讯作者：
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影响因子：
5.8
作者：
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通讯作者：
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