2012年8月25日 訊 /生物谷BIOON/ --根據(jù)一項發(fā)表在Journal of Clinical Oncology雜志上的研究證實：一線治療轉(zhuǎn)移性黑色素瘤的藥物白細(xì)胞介素21（IL-21）的總體反應(yīng)率（ORR）為22.5％,，但其值得進(jìn)一步研究,。
多倫多Sunnybrook Odette癌癥中心Teresa M. Petrella醫(yī)學(xué)博士和同事進(jìn)行了一項2期臨床實驗，該多中心臨床研究以評估IL-21對轉(zhuǎn)移性黑色素瘤患者的療效和安全性,。其中兩組患者種,，30例每天靜脈注射30微克/千克治療,，3例每天接受靜脈注射50微克/千克治療，設(shè)置8周為一周期,，在第一,、三、五周給予治療,，每星期為期5天,。第三組中7例每天接受50微克/千克，每星期為期5天,，在第1和3周給予治療,，設(shè)置6周為一周期。
研究人員發(fā)現(xiàn),，治療相關(guān)的不良反應(yīng)包括疲勞,、皮疹、腹瀉,、惡心,、肌痛。總體反應(yīng)率ORR為22.5％,，9例患者病情出現(xiàn)部分緩解,，16例患者出現(xiàn)病情穩(wěn)定。所有患者出現(xiàn)治療應(yīng)答的響應(yīng)時間中位數(shù)為5.3個月,。治療響應(yīng)不依賴于BRAF突變狀態(tài)或IL-21受體的表達(dá),。總體而言,，中位無進(jìn)展生存期為4.3個月,，中位總生存期為12.4個月。在這個試驗中觀察其劑量和用藥方案對抗腫瘤活性的影響,，雖然接受治療參與臨床實驗的人數(shù)很少,，但作者表示：其治療效果即患者對治療的響應(yīng)在所有發(fā)病部位包括皮膚、淋巴結(jié),、肺,、肝和其他內(nèi)臟器官都出現(xiàn)了。兩位研究作者稱其科研經(jīng)費從ZymoGenetics公司獲贈.（生物谷：Bioon.com）
編譯自：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.
