Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients
Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients
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DOI：
10.1200/jco.2004.11.035
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发表时间：
2004-11-15
影响因子：
45.3
通讯作者：
Sondel, P
中科院分区：
文献类型：
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作者：
King, DM;Albertini, MR;Sondel, P
目的评价EMD 273063（hu14.18-IL-2）治疗转移性黑色素瘤患者的安全性、毒性、体内免疫激活和最大耐受剂量（MTD）。EMD 273063在第1周的第1、2和3天静脉输注4小时。病情稳定或消退的患者可在第5周接受第二疗程治疗。评估的剂量水平为0.8，1.6，3.2，4.8，6.0和7.5毫克/平方米（2）/天。结果19 33例患者完成了第1个疗程，病情稳定，并继续接受疗程2。8例患者在完成疗程2时病情稳定。3级不良事件包括低磷血症（11例患者）、高血糖症（3例患者）、低血压（2例患者）、血小板减少症（1例患者）、缺氧（3例患者）、肝转氨酶升高（2例患者）和高胆红素血症（1例患者）。在52个疗程中的17个疗程中，治疗相关关节痛和/或肌痛需要阿片类药物。未观察到4级不良事件。MTD时的剂量限制性毒性包括缺氧、低血压和AST/ALT升高。基于IL-2或抗GD 2 mAb的既往研究，预期3级毒性，并且所有毒性均消退。免疫激活诱导，如测量淋巴细胞增多，增加外周血自然杀伤细胞活性，细胞数量，并增加血清水平的可溶性α链的IL-2 receptor complex.ConclusionTreatment与免疫细胞因子EMD 273063诱导免疫激活，并与可逆的临床毒性在7.5 mg/m2/d的MTD在黑色素瘤患者。(C)2004年，美国临床肿瘤学会。
PurposeTo evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma.Patients and MethodsThirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m(2)/d.ResultsNineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex.ConclusionTreatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m(2)/d in melanoma patients. (C) 2004 by American Society of Clinical Oncology.