CPX-1脂质体注射剂在晚期实体瘤患者中的安全性，药代动力学和功效。,Clinical Cancer Research

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CPX-1脂质体注射剂在晚期实体瘤患者中的安全性，药代动力学和功效。
Clinical Cancer Research ( IF 10.0 ) Pub Date : 2009 Jan 15 , DOI: 10.1158/1078-0432.ccr-08-0515
Gerald Batist ₁ , Karen A. Gelmon ₂ , Kim N. Chi ₂ , Wilson H. Miller ₁ , Stephen K.L. Chia ₂ , Lawrence D. Mayer ₃ , Christine E. Swenson ₃ , Andrew S. Janoff ₃ , Arthur C. Louie ₃

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用途：CPX-1是伊立替康和氟尿苷的新型脂质体包裹制剂，旨在延长输注后两种药物的体外优化协同摩尔比。这项开放标签，单臂，剂量递增的I期研究旨在确定晚期实体瘤患者中CPX-1的最大耐受剂量和药代动力学。实验设计：患者在28天内每14天以90、30、60、100、150、210或270单位/ m 2的剂量接受CPX-1（1单位= 1毫克伊立替康+ 0.36毫克氟尿苷）周期。在第1周期的第1天和第15天收集药代动力学样品。结果：33例患者入组，治疗并进行了安全性评估；评价30例患者的反应。血浆伊立替康与氟尿苷的摩尔比为1：1，维持8至12小时。3/4级毒性包括腹泻（24.2％），中性粒细胞减少症（12.1％）和低钾血症（12.1％）；1例患者（270单位/ m（2））死于持续性腹泻，导致脱水和肾衰竭（5级）。通过实体瘤反应评估标准评估的25位受试者中有3位（12％）发生了部分反应。9例大肠癌患者中有6个月的无进展生存期超过6个月。在15例结直肠癌患者（其中10例曾接受伊立替康治疗）中，计算出的无进展生存期中位数为5.4个月；11名患者（72.7％）实现了疾病控制，而2名患者（13％）出现了部分缓解。结论：晚期实体瘤患者对门诊CPX-1的耐受性良好，并具有抗肿瘤活性。未来研究的推荐剂量为210单位/ m（2）。

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Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors.

PURPOSE: CPX-1 is a novel, liposome-encapsulated formulation of irinotecan and floxuridine designed to prolong in vitro optimized synergistic molar ratios of both drugs postinfusion. This open-label, single-arm, dose-escalating phase I study was designed to determine the maximum tolerated dose and pharmacokinetics of CPX-1 in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients received CPX-1 at 30, 60, 100, 150, 210, or 270 units/m(2) (1 unit = 1 mg irinotecan + 0.36 mg floxuridine) infused over 90 minutes every 14 days in 28-day cycles. Pharmacokinetic samples were collected on days 1 and 15 of cycle 1. RESULTS: Thirty-three patients were enrolled, treated, and evaluated for safety; 30 patients were evaluated for response. A 1:1 plasma irinotecan to floxuridine molar ratio was maintained for 8 to 12 hours. Grade 3/4 toxicities included diarrhea (24.2%), neutropenia (12.1%), and hypokalemia (12.1%); 1 patient (270 units/m(2)) died of persistent diarrhea, which led to dehydration and renal failure (grade 5). Partial response occurred in 3 (12%) of the 25 subjects evaluated through Response Evaluation Criteria in Solid Tumors. Progression-free survival lasting >6 months occurred in 9 patients, 6 with colorectal cancer. Among 15 colorectal cancer patients (10 with prior irinotecan), the calculated median progression-free survival was 5.4 months; 11 patients (72.7%) achieved disease control and 2 patients (13%) had partial response. CONCLUSIONS: Outpatient CPX-1 was well tolerated and antitumor activity was shown in patients with advanced solid tumors. The recommended dose for future studies is 210 units/m(2). This is the first clinical evaluation of fixed drug ratio dosing designed to maintain synergistic molar ratios for enhanced therapeutic benefit.

更新日期：2017-01-31

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