Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: The Eastern Cooperative Oncology Group trial EST 1684
Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: The Eastern Cooperative Oncology Group trial EST 1684
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DOI：
10.1200/jco.1996.14.1.7
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发表时间：
1996-01-01
影响因子：
45.3
通讯作者：
Blum, RH
中科院分区：
文献类型：
--
作者：
Kirkwood, JM;Strawderman, MH;Blum, RH
目的：干扰素α-2b（IFN（α-2b）在转移性黑素瘤中表现出抗肿瘤活性，并且在此基础上，已被评价为深部原发性（T4）或区域转移性（N1）黑素瘤手术后的辅助疗法。干扰素α-2b的随机对照研究（先灵葆雅，凯尼尔沃思，NJ）以最大耐受剂量20 MU/m2/d静脉注射（IV）1个月和10 MU/m2每周皮下注射（SC）3次给药由美国东部肿瘤协作组（ECOG）对287例患者进行为期48周的治疗与观察。无复发生存期显著延长（P =.0023，单侧）和总生存期延长（P = 0.0237，单侧），该试验现已成熟，中位随访时间为6.9年，治疗对复发率的影响在治疗间隔的早期最为显著。该试验中的治疗的总体益处通过肿瘤负荷和存在或不存在显微镜下不可触及和可触及的区域淋巴结转移进行分层分析。在淋巴结阳性分层中，用IFN（α-2b）治疗的益处最大，IFN α-2b的毒性在大多数患者中需要剂量调整，但是在大于或等于预定剂量的80%的治疗在大多数患者中通过IV治疗阶段是可行的，并且对于超过3个月的SC维持治疗，在治疗的第四个月后由于毒性而停止治疗是罕见的。IFN α-2b延长了高危切除黑色素瘤患者的无复发间期和总生存期中位无病生存期的增加（1 - 1.7年）和总生存期从2.8年到3.8年）与IFN治疗后持续无病患者比例的42%改善相关（从26%到37%）相比，观察，IFN α-2b是第一个药物显示出显着的好处，在无复发和总生存率的高风险黑色素瘤患者在一项随机对照试验。(C)1996年，美国临床肿瘤学会。
Purpose: Interferon alfa-2b (IFN(alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.Methods: A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m(2)/d intravenously (IV) for 1 month and 10 MU/m(2) three rimes per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients.Results: A significant prolongation of relapse-free survival(P =.0023, one-sided) and prolongation of overall survival (P =.0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years, The impact of treatment on relapse rate is most pronounced early during the treatment interval, The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis, The benefit of therapy with IFN(alpha-2b was greatest among node-positive strata, Toxicity of IFN(alpha-2b required dose modification in the majority of patients, but treatment at greater than or equal to 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy, Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy.Conclusion: IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease free survival (from 1 to 1,7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation, IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial. (C) 1996 by American Society of Clinical Oncology.