Barth A, Morton D L
John Wayne Cancer Institute, Saint John's Hospital and Health Center, Santa Monica, CA 90404.
Cancer. 1995 Jan 15;75(2 Suppl):726-34. doi: 10.1002/1097-0142(19950115)75:2+<726::aid-cncr2820751417>3.0.co;2-r.
Adequate wide excision of a primary cutaneous melanoma is associated with a 10-year cure rate of 85% when the tumor's depth is less than 1.5 mm (American Joint Committee on Cancer [AJCC] Stage I). However, 50% of patients with deep (> 4 mm) primary melanomas, 60-85% of those with regional lymph node metastases (AJCC Stage III), and 95% of those with metastases to distant sites (AJCC Stage IV) will experience recurrence, which is associated with a dismal prognosis. Adjuvant therapy of melanoma assumes that treatment will be more effective when the tumor burden is small. In the 1970s and 1980s, randomized trials tested the efficacy of chemotherapy, nonspecific immunotherapy, levamisole, and regional perfusion therapy in patients with AJCC Stage II and III melanoma. Dacarbazine (DTIC) alone or in combination with other chemotherapeutic drugs or with nonspecific immunotherapy did not significantly improve disease free or overall survival. Of the four levamisole trials, only the study conducted by the National Cancer Institute of Canada revealed a reduction in recurrence and mortality; however, this reduction was not significant by multivariate analysis. The value of regional perfusion therapy following resection of high risk extremity melanomas is currently being determined by multiinstitutional studies conducted by the World Health Organization and the North American Perfusion Group. Multi-institutional trials also are examining the adjuvant role of interferon-alpha in patients with deep (> 3 mm) primary melanomas or positive regional lymph nodes; results should reveal its optimum dose and duration of treatment (3 x 10(6) U for > or = 2 years versus 10 x 10(6) U/m2 for 1 year, subcutaneously 3 times a week) and its impact on survival. A randomized trial of interferon-gamma undertaken by the Southwest Oncology Group was discontinued after interim analysis indicated an adverse effect. Phase II trials indicate that active specific immunotherapy can alter the natural course of AJCC Stage III and IV melanoma following surgical resection of nodal or distant metastases. Upcoming results of Phase III trials will establish the role of active specific immunotherapy for adjuvant treatment of patients with resected AJCC Stage III and IV melanoma.
当原发性皮肤黑色素瘤深度小于1.5毫米时（美国癌症联合委员会[AJCC]I期），充分广泛切除后的10年治愈率为85%。然而，50%的原发性黑色素瘤深度超过4毫米的患者、60 - 85%有区域淋巴结转移的患者（AJCC III期）以及95%有远处转移的患者（AJCC IV期）会出现复发，这与预后不良相关。黑色素瘤的辅助治疗基于肿瘤负荷较小时治疗会更有效的假设。在20世纪70年代和80年代，随机试验测试了化疗、非特异性免疫疗法、左旋咪唑和区域灌注疗法对AJCC II期和III期黑色素瘤患者的疗效。单独使用达卡巴嗪（DTIC）或与其他化疗药物联合使用或与非特异性免疫疗法联合使用，均未显著改善无病生存期或总生存期。在四项左旋咪唑试验中，只有加拿大国家癌症研究所进行的研究显示复发率和死亡率有所降低；然而，经多变量分析，这种降低并不显著。世界卫生组织和北美灌注组正在通过多机构研究确定高危肢体黑色素瘤切除术后区域灌注疗法的价值。多机构试验也在研究α干扰素对原发性黑色素瘤深度超过3毫米或区域淋巴结阳性患者的辅助作用；结果应能揭示其最佳剂量和治疗持续时间（≥2年，3×10⁶单位皮下注射，每周3次，与1年，10×10⁶单位/平方米皮下注射，每周3次相比）及其对生存的影响。西南肿瘤学组进行的一项γ干扰素随机试验在中期分析显示有不良影响后停止。II期试验表明，主动特异性免疫疗法可改变AJCC III期和IV期黑色素瘤在手术切除淋巴结或远处转移后的自然病程。即将公布的III期试验结果将确定主动特异性免疫疗法在辅助治疗已切除AJCC III期和IV期黑色素瘤患者中的作用。
