干扰素α-2b辅助治疗高危切除性皮肤黑色素瘤：东部肿瘤协作组试验EST 1684

Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial EST 1684.

作者信息

Kirkwood J M, Strawderman M H, Ernstoff M S, Smith T J, Borden E C, Blum R H

机构信息

Division of Medical Oncology, University of Pittsburgh, PA 15213-2582, USA.

出版信息

J Clin Oncol. 2023 Jan 20;41(3):425-435. doi: 10.1200/JCO.22.02264.

DOI:10.1200/JCO.22.02264

PMID:36649675

Abstract

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/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times 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 > or = 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.

摘要

目的

干扰素α-2b（IFNα-2b）在转移性黑色素瘤中显示出抗肿瘤活性，并在此基础上被评估为深部原发性（T4）或区域转移性（N1）黑色素瘤手术后的辅助治疗。

方法

东部肿瘤协作组（ECOG）对287例患者进行了一项随机对照研究，比较了最大耐受剂量为20 MU/m²/d静脉注射（i.v.）1个月和10 MU/m²皮下注射（SC）每周3次共48周的IFNα-2b（先灵葆雅公司，新泽西州肯尼沃思）与观察治疗的效果。

结果

在本试验中，IFNα-2b治疗观察到无复发生存期显著延长（P = 0.0023，单侧）和总生存期延长（P = 0.0237，单侧），目前该试验已成熟，中位随访时间为6.9年。治疗对复发率的影响在治疗期间早期最为明显。本试验中治疗的总体获益按肿瘤负荷以及有无微小不可触及和可触及的区域淋巴结转移进行分层分析。IFNα-2b治疗在淋巴结阳性分层中获益最大。IFNα-2b的毒性需要在大多数患者中调整剂量，但在大多数患者中，在治疗的IV期以及超过3个月的皮下维持治疗期间，按计划剂量的≥80%进行治疗是可行的。治疗4个月后因毒性而停药的情况很少见。

结论

IFNα-2b可延长高危切除黑色素瘤患者的无复发生存期和总生存期。该疗法使无病生存期（从中位1年延长至1.7年）和总生存期（从中位2.8年延长至3.8年）增加，与观察治疗相比，接受IFN治疗后持续无病的患者比例提高了42%（从26%提高到37%）。IFNα-2b是首个在随机对照试验中显示对高危黑色素瘤患者的无复发生存期和总生存期有显著获益的药物。