Unit of Melanoma, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy.
Oncology Division, Department of Clinical Medicine, University "Federico II" of Naples, Italy.
Cytokine Growth Factor Rev. 2015 Apr;26(2):203-12. doi: 10.1016/j.cytogfr.2014.11.008. Epub 2014 Nov 22.
Interferon (IFN) and PEG-IFN are the only drugs approved as adjuvant therapy in patients with melanoma at high-risk of recurrence after surgical resection. Several clinical trials of adjuvant IFN, using different doses and durations of therapy, have been conducted in these patients. Results generally suggest relapse-free survival and overall survival benefits; however, questions over the optimal dose and duration of treatment and concerns over toxicity have limited its use. IFN exerts its biological activity in melanoma via multiple mechanisms of action, most of which can be considered as indirect immunomodulatory effects. As such, IFN may also be of benefit in the neoadjuvant setting, where it may have a role in melanoma patients with locally advanced disease for whom immediate surgical excision is not possible. However, this has not been well studied. The use of IFN in patients with metastatic melanoma is controversial, with limited data and no convincing evidence of a survival benefit. However, IFN therapy combined with novel biological and immunotherapies offers the potential for a synergistic effect and improved clinical outcomes. Predictive and prognostic factors to better select melanoma patients for IFN treatment have been identified (e.g. disease stage, ulceration, various cytokines) and may also enhance its therapeutic efficacy, but their incorporation into the clinical decision-making process requires validation in prospective trials. In conclusion, the modest efficacy of IFN shown in clinical trials is largely a reflection of differences in response between patients. Despite advancements in the understanding of its biological mechanisms of action, the huge potential of IFN remains to be fully explored and utilized in patients with melanoma.
干扰素 (IFN) 和聚乙二醇干扰素 (PEG-IFN) 是唯一被批准用于手术切除后有高复发风险的黑色素瘤患者辅助治疗的药物。已经在这些患者中进行了几项辅助 IFN 的临床试验，使用了不同的剂量和治疗持续时间。结果普遍提示无复发生存和总生存获益；然而，关于最佳剂量和治疗持续时间的问题以及对毒性的担忧限制了其应用。IFN 通过多种作用机制在黑色素瘤中发挥其生物学活性，其中大多数可被认为是间接免疫调节作用。因此，IFN 在新辅助治疗中也可能有益，它可能在局部晚期疾病患者中发挥作用，这些患者无法立即进行手术切除。然而，这尚未得到很好的研究。IFN 在转移性黑色素瘤患者中的应用存在争议，数据有限，且无令人信服的生存获益证据。然而，IFN 治疗与新型生物和免疫疗法联合使用可能具有协同作用并改善临床结局。已经确定了更好地选择接受 IFN 治疗的黑色素瘤患者的预测和预后因素（例如疾病分期、溃疡、各种细胞因子），并且也可能增强其治疗效果，但将其纳入临床决策过程需要在前瞻性试验中验证。总之，临床试验中 IFN 的疗效适度，主要反映了患者之间的反应差异。尽管对其作用机制的生物学理解取得了进展，但 IFN 的巨大潜力仍有待充分探索和利用于黑色素瘤患者。
