Isolated limb perfusion for extremity soft-tissue sarcomas, in-transit metastases, and other unresectable tumors: credits, debits, and future perspectives.
Isolated limb perfusion for extremity soft-tissue sarcomas, in-transit metastases, and other unresectable tumors: credits, debits, and future perspectives.
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DOI：
10.1007/s11912-001-0090-8
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发表时间：
2001-07-01
影响因子：
4.7
通讯作者：
ten Hagen, T L
中科院分区：
文献类型：
--
作者：
Eggermont, A M;ten Hagen, T L
美法仑的隔离肢体灌注（ILP）对黑色素瘤的转移是有效的，但对威胁肢体的肢体肉瘤的治疗失败。肿瘤坏死因子-α（TNF）的出现彻底改变了这种状况。现在，ILP联合TNF +美法仑是一种非常成功的预防截肢的治疗方法。在一项多中心欧洲试验中，ILP联合TNF +美法仑治疗被独立审查委员会认为不可切除的威胁肢体的软组织肉瘤患者的有效率为76%，保肢率为71%，导致TNF在欧洲获得批准。我们还报道了这种疗法在治疗大体积黑色素瘤、多灶性皮肤癌和耐药骨肉瘤方面的成功。高剂量TNF破坏肿瘤血管系统，最重要的是，它使肿瘤选择性药物（即美法仑和多柔比星）吸收增强三倍至六倍。在用TNF和美法仑隔离肝灌注后，在血管化良好的肝转移中观察到类似的协同作用。新的（血管活性）药物和作用机制以及与化疗的相互作用正在开发中。ILP也是腺病毒载体介导的基因治疗的一种有前途的治疗方式。目前正在进行ILP的许多临床I/II期评价。
Isolated limb perfusion (ILP) with melphalan is effective against melanoma in-transit metastases but has failed in the treatment of limb-threatening extremity sarcomas. Tumor necrosis factor-alpha (TNF) has changed this situation completely. Now, ILP with TNF + melphalan is a very successful treatment to prevent amputation. In a multicenter European trial, ILP with TNF + melphalan resulted in a 76% response rate and a 71% limb salvage rate in patients with limb-threatening soft-tissue sarcomas, deemed unresectable by independent review committees, leading to approval of TNF in Europe. We have also reported on the success of this regimen against bulky melanomas, multifocal skin cancers, and drug-resistant bony sarcomas. High-dose TNF destructs tumor vasculature, and, most importantly, it enhances tumor-selective drug uptake (ie, melphalan and doxorubicin) by threefold to sixfold. Similar synergy is observed in well-vascularized liver metastases after isolated hepatic perfusion with TNF and melphalan. New (vasoactive) drugs and mechanisms of action and interaction with chemotherapy are in development. ILP is also a promising treatment modality for adenoviral vector-mediated gene therapy. Many clinical phase I/II evaluations in ILP are now underway.