2012年8月25日 讯 /生物谷BIOON/ --根据一项发表在Journal of Clinical Oncology杂志上的研究证实：一线治疗转移性黑色素瘤的药物白细胞介素21（IL-21）的总体反应率（ORR）为22.5％，但其值得进一步研究。
多伦多Sunnybrook Odette癌症中心Teresa M. Petrella医学博士和同事进行了一项2期临床实验，该多中心临床研究以评估IL-21对转移性黑色素瘤患者的疗效和安全性。其中两组患者种，30例每天静脉注射30微克/千克治疗，3例每天接受静脉注射50微克/千克治疗，设置8周为一周期，在第一、三、五周给予治疗，每星期为期5天。第三组中7例每天接受50微克/千克，每星期为期5天，在第1和3周给予治疗，设置6周为一周期。
研究人员发现，治疗相关的不良反应包括疲劳、皮疹、腹泻、恶心、肌痛。总体反应率ORR为22.5％，9例患者病情出现部分缓解，16例患者出现病情稳定。所有患者出现治疗应答的响应时间中位数为5.3个月。治疗响应不依赖于BRAF突变状态或IL-21受体的表达。总体而言，中位无进展生存期为4.3个月，中位总生存期为12.4个月。在这个试验中观察其剂量和用药方案对抗肿瘤活性的影响，虽然接受治疗参与临床实验的人数很少，但作者表示：其治疗效果即患者对治疗的响应在所有发病部位包括皮肤、淋巴结、肺、肝和其他内脏器官都出现了。两位研究作者称其科研经费从ZymoGenetics公司获赠.（生物谷：Bioon.com）
编译自：Metastatic melanoma responds to first-line interleukin-21
doi:10.1200/JCO.2011.40.0655
PMC:
PMID:
Interleukin-21 Has Activity in Patients With Metastatic Melanoma: A Phase II Study
Teresa M. Petrella, Richard Tozer, Karl Belanger, Kerry J. Savage, Ralph Wong, Michael Smylie, Suzanne Kamel-Reid, Victor Tron, Bingshu E. Chen, Naomi N. Hunder, Linda Hagerman, Wendy Walsh and Elizabeth A. Eisenhauer
Purpose We report a multicenter phase II study of patients with metastatic melanoma (MM), evaluating the efficacy, toxicity, progression-free survival (PFS), immunogenicity, and biomarker profile of interleukin-21 (IL-21).
Patients and Methods Patients with no prior systemic therapy and with limited-disease MM were treated with IL-21 by using three different dosing regimens. Cohort 1 received 50 μg/kg per day by outpatient intravenous bolus injection for 5 days of each week during weeks 1, 3, and 5 of an 8-week cycle. Cohort 2 received 30 μg/kg per day on the same schedule, and cohort 3 received 50 μg/kg per day for 5 days of each week during weeks 1 and 3 of a 6-week cycle.
Results Forty patients were enrolled: three in cohort 1, 30 in cohort 2, and seven in cohort 3. Two patients in cohort 1 and four in cohort 3 had dose-limiting toxicities; all other patients were treated with a dose of 30 μg/kg per day. Common adverse events were fatigue, rash, diarrhea, nausea, and myalgia. Overall response rate (ORR) was 22.5%, with nine confirmed partial responses (median response duration, 5.3 months); 16 had stable disease (median response duration, 5.3 months). ORR did not appear to depended on IL-21 receptor expression or BRAF mutation status. The median PFS was 4.3 months and median overall survival (OS) was 12.4 months (95% CI, 10.09 to 17.81 months).
Conclusion The ORR to IL-21 is 22.5% for first-line MM and warrants further investigation. The favorable PFS and OS suggest that this is an active agent in comparison to both historical NCIC Clinical Trials Group data and data from meta-analysis of Cooperative Group phase II trials.
