Rossi Carlo Riccardo, Mocellin Simone, Pilati Pierluigi, Foletto Mirto, Campana Luca, Quintieri Luigi, De Salvo Gian Luca, Lise Mario
Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
Ann Surg Oncol. 2005 May;12(5):398-405. doi: 10.1245/ASO.2005.12.038. Epub 2005 Mar 29.
Tumor necrosis factor (TNF)-alpha-based hyperthermic isolated limb perfusion (HILP) is one of the most active available approaches for locally advanced soft tissue sarcomas (STS) of the limbs. The aim of this study was to investigate the anticancer activity of a novel drug regimen including doxorubicin (DXR) and low-dose TNF-alpha.
HILP with low-dose TNF-alpha (1 mg) and DXR (8.5 mg/L of limb volume) was given to 21 patients with limb-threatening STS: 14 had primary and 7 had recurrent STS, most of which were high grade (grade 1, n = 3; grade 2, n = 6; grade 3, n = 12). Resection of the tumor remnant was performed 6 to 8 weeks after HILP. TNF-alpha concentrations in plasma and perfusate were measured throughout perfusion.
A major tumor response was observed at histology and clinical evaluation in 90% and 62% of patients, respectively. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 71% and 81% of cases, respectively. Fourteen patients had moderate regional toxicity, which was resolved in all cases. One patient had severe limb toxicity, which did not require amputation. Systemic side effects were minimal, and there were no postoperative deaths. The perfusate/plasma area under the curve ratio for TNF-alpha was 56.
HILP with low-dose TNF-alpha and DXR seems to be an active neoadjuvant drug regimen against limb-threatening STS. This therapeutic approach can achieve high limb-sparing surgery rates with acceptable local and negligible systemic toxicity.
基于肿瘤坏死因子（TNF）-α的热灌注隔离肢体疗法（HILP）是治疗肢体局部晚期软组织肉瘤（STS）最有效的现有方法之一。本研究的目的是探讨一种包含阿霉素（DXR）和低剂量TNF-α的新型药物方案的抗癌活性。
对21例肢体受到威胁的STS患者进行低剂量TNF-α（1毫克）和DXR（8.5毫克/肢体体积升）的HILP治疗：14例为原发性STS，7例为复发性STS，其中大多数为高级别（1级，n = 3；2级，n = 6；3级，n = 12）。在HILP治疗6至8周后切除肿瘤残余组织。在整个灌注过程中测量血浆和灌注液中的TNF-α浓度。
分别在90%和62%的患者中观察到组织学和临床评估的主要肿瘤反应。中位随访30个月后，分别有71%和81%的病例实现了保肢和局部疾病控制。14例患者有中度局部毒性，所有病例均得到缓解。1例患者有严重的肢体毒性，但无需截肢。TNF-α的灌注液/血浆曲线下面积比为56。
低剂量TNF-α和DXR的HILP似乎是一种针对肢体受到威胁的STS的有效新辅助药物方案。这种治疗方法可以实现高保肢手术率，且局部毒性可接受，全身毒性可忽略不计。
