Kirkwood J M
Division of Medical Oncology, University of Pittsburgh Medical Center, Pennsylvania 15213-2582, USA.
Eur J Cancer. 1998 Jul;34 Suppl 3:S12-7. doi: 10.1016/s0959-8049(97)10159-9.
Until recently, the prognosis of patients with deep primary melanomas or regionally metastatic nodal disease has been poor, with 5-year survival rates of 25-50%. The results of the Eastern Cooperative Oncology Group (ECOG) trial 1684 represent the first evidence of effective adjuvant therapy for these patients. Interferon alfa-2b (IFN-alpha 2b) administered at maximally tolerated doses for 1 year significantly improved both relapse-free and overall survival. The impact of interferon therapy was observed early during treatment and the effect was durable. The results of this trial represent a breakthrough in the treatment of high-risk resected cutaneous melanoma and identify the new reference standard for new cytokines, vaccines and combinations. The favourable results provide a strong impetus for redoubled research into immunotherapy for treatment of melanoma. Specifically, ganglioside vaccines have been identified that induce antibody responses and may affect patient outcome and peptide/protein vaccines that are recognised by the T-cell have been identified in large numbers. ECOG and the U.S. Intergroup are conducting a phase III trial (E1694) that compares GM2 vaccine to IFN-alpha 2b and a phase II trial evaluating concurrent or sequential use of interferon and vaccines for patients with resectable melanoma. They are also planning phase II trials of peptides for patients with metastatic unresectable melanoma. Laboratory analyses of the immune responses induced by IFN and the several vaccines are anticipated to reveal the fundamental immune mechanisms that are important for relapse-free survival and immunological control of melanoma.
直到最近，患有深部原发性黑色素瘤或区域转移性淋巴结疾病的患者预后一直很差，5年生存率为25%至50%。东部肿瘤协作组（ECOG）1684试验的结果是这些患者有效辅助治疗的首个证据。以最大耐受剂量给予干扰素α-2b（IFN-α 2b）1年，显著改善了无复发生存率和总生存率。在治疗早期就观察到了干扰素治疗的效果，且效果持久。该试验结果代表了高危切除性皮肤黑色素瘤治疗的突破，并确定了新的细胞因子、疫苗及联合治疗的新参考标准。这些良好结果为黑色素瘤免疫治疗的进一步研究提供了强大动力。具体而言，已鉴定出可诱导抗体反应并可能影响患者预后的神经节苷脂疫苗，以及大量被T细胞识别的肽/蛋白疫苗。ECOG和美国肿瘤协作组正在进行一项III期试验（E1694），比较GM2疫苗与IFN-α 2b，以及一项II期试验，评估可切除黑色素瘤患者同时或序贯使用干扰素和疫苗的情况。他们还计划对转移性不可切除黑色素瘤患者进行肽的II期试验。预计对IFN和几种疫苗诱导的免疫反应进行实验室分析，将揭示对黑色素瘤无复发生存和免疫控制至关重要的基本免疫机制。
