Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: A multicenter trial
Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: A multicenter trial
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DOI：
10.1200/jco.1996.14.10.2653
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发表时间：
1996-10-01
影响因子：
45.3
通讯作者：
Lejeune, FJ
中科院分区：
文献类型：
--
作者：
Eggermont, AMM;Koops, HS;Lejeune, FJ
目的：16确定与干扰素-γ（IFN）和美法仑组合的肿瘤坏死因子-α（TNF）的隔离肢体灌注（ILP）作为诱导疗法以使患有不可切除的肢体软组织肉瘤（STS）的患者的肿瘤可切除并避免截肢的功效。在55例患者的30个肉瘤中，原发性肉瘤和25个复发性肉瘤中，有48个高级别肉瘤和7个I级肉瘤这一系列患者的组成是不寻常的：13名患者（24%）患有多灶性原发性肉瘤或多发性复发肿瘤;肿瘤非常大（中位数，18厘米）和9名患者（16%）有已知的全身转移，IFN皮下注射前2天的ILP与TNF，IFN，和美法仑。ILP后2 ~ 3个月行肿瘤残留的延迟边缘切除术。结果：87%的患者肿瘤有明显的缓解，大部分患者可切除。10例（18%）完全缓解（CR），35例（64%）部分缓解（PR），10例（18%）无变化（NC），最终结局按临床和病理学缓解定义如下：20例（36%）CR、28例（51%）PR和7例（13%）NC，84%的患者实现了保肢（随访时间，20+至50+个月）。在39例患者中，在ILP后进行了肿瘤残留（n = 31）或2 - 8个肿瘤（n = 8）的切除; 5例（13%）发生局部复发，未行切除术（多发肿瘤或全身转移），局部复发频繁（16例中的5例），但由于患者死于全身性疾病，通常可以实现保肢，局部毒性有限，全身毒性为极轻微至中度，无毒性死亡，组织学显示出血性坏死;血管造影显示选择性破坏肿瘤相关vessel.Conclusion：ILP与TNF，IFN，和马法兰是一种安全，高效的诱导生物化疗程序，可以实现保肢患者不可切除的四肢STS，TNF是一种积极的抗癌药物，在人类的设置ILP。
Purpose: 16 determine the efficacy of isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF) in combination with interferon-gamma (IFN) and melphalan as induction therapy to render tumors resectable and avoid amputation in patients with nonresectable extremity soft tissue sarcomas (STS).Patients and Methods: Among 55 patients with 30 sarcomas, primary and 25 recurrent sarcomas, there were 48 high-grade and seven grade I sarcomas (very large, recurrent, or multiple), The composition of this series of patients is unusual: 13 patients (24%) had multifocal primary sarcomas or multiple recurrent tumors; tumors were very large (median, 18 cm); and nine patients (16%) had known systemic metastases, IFN was administered subcutaneously on the 2 days before ILP with TNF, IFN, and melphalan. A delayed marginal resection of the tumor remnant was usually performed 2 to 3 months after ILP.Results: A major tumor response was seen in 87% of patients and rendered the sarcomas resectable in most cases, Clinical response rates were as follows: 10 (18%) completes responses (CRs), 35 (64%) partial responses (PRs), and 10 (18%) no change (NC), Final outcome was defined as follows by clinical and pathologic response: 20 (36%) CRs, 28 (51%) PRs, and seven (13%) NC, Limb salvage was achieved in 84% (follow-up duration, 20+ to 50+ months). In 39 patients, resection of the tumor remnant (n = 31) or of two to eight tumors (n = 8) after ILP was performed; local recurrence developed in five (13%), When no resection was performed (multiple tumors or systemic metastases), local recurrences were frequent (five of 16), but limb salvage was often achieved as patients died of systemic disease, Regional toxicity was limited and systemic toxicity minimal to moderate with no toxic deaths, Histology showed hemorrhagic necrosis; angiographies showed selective destruction of tumor-associated vessels.Conclusion: ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS, TNF is an active anticancer drug in humans in the setting of ILP.