Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors
Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors
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DOI：
10.1097/cad.0000000000000409
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发表时间：
2016-11-01
影响因子：
2.3
通讯作者：
Soria, Jean-Charles
中科院分区：
文献类型：
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作者：
Aspeslagh, Sandrine;Awada, Ahmad;Soria, Jean-Charles
这项I期试验评估了海洋衍生环磷脂肽和贝伐单抗在晚期癌症患者中的毒性分布和最大耐受量。13例患者接受3个剂量水平(2.8 mg/m(2)，n=3；3.8 mg/m(2)，n=4；4.8 mg/m(2)，n=6)的贝伐单抗(10 mg/kg)治疗。两种药物均在28天周期的d1和d15静脉给药。所有13名患者的安全性和毒性均可评估。在接受最大剂量治疗的6名患者中，有2名患者出现了剂量限制毒性(普利替丁4.8 mg/m(2)和贝伐单抗10 mg/kg)，包括3级疲劳、3级肌肉疼痛和2级2/3丙氨酸转氨酶升高，持续超过7天或导致随后的周期延迟超过2周(n=1)。普利迭酶联合贝伐单抗的推荐剂量为3.8 mg/m(2)，贝伐单抗10 mg/kg，每2周一次。最常见的与治疗相关的不良事件是恶心、呕吐、疲劳、鼻出血和头痛。相关的血液学毒性最小。目的：没有观察到疾病反应；但是，在4例结直肠癌、肾癌和宫颈癌患者中观察到了稳定的疾病(>；3个月)。普利替丁与贝伐单抗联合应用是可行的。病情稳定是获得的最好反应。
This phase I trial evaluated the toxicity profile and maximum tolerated dose of the combination between the marine derived cyclodepsipeptide plitidepsin and bevacizumab in advanced cancer patients. Thirteen patients were enrolled and treated with plitidepsin at three dose levels (2.8mg/m(2), n=3; 3.8mg/m(2), n=4; and 4.8mg/m(2), n=6) with a fixed dose of bevacizumab (10mg/kg). Both agents were administered intravenously at D1 and D15 of a 28-day cycle. All 13 patients were evaluable for safety and toxicity. Dose-limiting toxicities occurred in two out of six patients treated at the maximum dose tested (plitidepsin 4.8mg/m(2) and bevacizumab 10mg/kg) and consisted of grade 3 fatigue, grade 3 myalgia, and two grade 2/3 alanine aminotransferase increases lasting for more than 7 days or leading to subsequent cycle delay greater than 2 weeks (n=1 each). The recommended dose for the combination of plitidepsin with bevacizumab was 3.8mg/m(2) for plitidepsin and 10mg/kg for bevacizumab every 2 weeks. Most frequent treatment-related adverse events were nausea, vomiting, fatigue, epistaxis, and headache. Relevant hematological toxicity was minimal. Objective disease responses were not observed; however, stable disease (>3 months) was observed in four patients with colorectal cancer, renal cancer, and cervical cancer. Combining plitidepsin with bevacizumab combination is feasible. Stable disease was the best response obtained.