Liénard D, Eggermont A M, Kroon B B, Schraffordt Koops H, Lejeune F J
Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland.
Semin Surg Oncol. 1998 Apr-May;14(3):202-9. doi: 10.1002/(sici)1098-2388(199804/05)14:3<202::aid-ssu3>3.0.co;2-c.
In advanced melanoma of the limbs with in-transit metastasis, melphalan with isolated limb perfusion (M-ILP) produces around 50% complete remissions (CR). The combination of melphalan with tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in isolated limb perfusion (TIM-ILP) gives around 80% CR. A prospective randomised phase II study compared 32 patients who received TIM-ILP with 32 patients who received TM-ILP (without IFNgamma). The overall remission rate (ORR) and the CR rate were superior with TIM-ILP as compared to TM-ILP, 100% vs. 91% and 78% vs. 69% respectively, but the differences are not significant. Given the efficacy of M-ILP on in-transit metastasis, the procedure was tested as an adjunct to surgery in high-risk (Breslow > or = 1.5 mm) primary melanoma of the limbs. Through the combined effort of the melanoma groups of the European Organization for Research and Treatment of Cancer (EORTC), the World Health Organization (WHO), and the North American Perfusion Group, 832 evaluable patients from 16 centres were entered in a phase III study. Median followup is 6.4 years. There was a trend for a longer disease-free interval after M-ILP. The difference is significant if the patients without elective lymph node dissection (ELND) are separately analysed, with a high significance in the 1.5 to 3 mm thickness subgroup. The occurrence of in-transit metastases was reduced from 6.6% to 3.3% by M-ILP. There was, however, no benefit of M-ILP in terms of survival. Prophylactic M-ILP cannot be recommended as a standard adjunct to surgery in high-risk primary limb melanoma. TIM-ILP or TM-ILP is a regional therapy with a very high regional response rate on melanoma in-transit metastasis.
在伴有途中转移的肢体晚期黑色素瘤中，美法仑隔离肢体灌注（M-ILP）可产生约50%的完全缓解（CR）。美法仑与肿瘤坏死因子-α（TNFα）和干扰素-γ（IFNγ）联合进行隔离肢体灌注（TIM-ILP）的完全缓解率约为80%。一项前瞻性随机II期研究将32例接受TIM-ILP的患者与32例接受TM-ILP（不含IFNγ）的患者进行了比较。与TM-ILP相比，TIM-ILP的总缓解率（ORR）和CR率更高，分别为100%对91%和78%对69%，但差异不显著。鉴于M-ILP对途中转移的疗效，该方法作为高危（Breslow≥1.5 mm）肢体原发性黑色素瘤手术的辅助手段进行了测试。通过欧洲癌症研究与治疗组织（EORTC）、世界卫生组织（WHO）和北美灌注组黑色素瘤研究小组的共同努力，来自16个中心的832例可评估患者进入了一项III期研究。中位随访时间为6.4年。M-ILP后无病间期有延长趋势。如果对未进行选择性淋巴结清扫（ELND）的患者进行单独分析，差异具有显著性，在厚度为1.5至3 mm的亚组中具有高度显著性。M-ILP使途中转移的发生率从6.6%降至3.3%。然而，M-ILP在生存方面并无益处。预防性M-ILP不能作为高危原发性肢体黑色素瘤手术的标准辅助手段推荐。TIM-ILP或TM-ILP是一种对黑色素瘤途中转移具有非常高区域缓解率的区域治疗方法。
