Hoekstra H J, van Ginkel R J
Division of Surgical Oncology, Department of Surgery, Groningen University Hospital, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Curr Opin Oncol. 2003 Jul;15(4):300-3. doi: 10.1097/00001622-200307000-00004.
High local drug concentrations can be achieved in a limb with minimal systemic toxicity with the technique of hyperthermic isolated limb perfusion (HILP). The currently most successful drugs are still Tumor Necrosis Factor alpha (TNFalpha) and melphalan. With HILP, as an induction chemotherapy treatment of locally advanced primarily irresectable soft tissue sarcomas of a limb, a limb salvage rate of 71% can be achieved, with a minimal treatment related morbidity. For the HILP is no upper age limit. Systemic inflammatory response syndrome is currently seldom seen. The exact working mechanisms of TNFalpha are still unknown. Experimental work is now directed to the development of drugs sensitizing the tumor vasculature to the effects of TNFalpha. In the clinical HILP setting are currently lower doses of TNFalpha in combination with melphalan investigated. Although multidrug resistance (MDR) is a major issue in effectiveness of chemotherapy in human cancer treatment, HILPs with TNFalpha and melphalan did not induce MDR in sarcomas. The future research in HILP with TNFalpha is directed in increasing tumor sensitivity for TNF with lowering the dosage without decreasing tumor response.
通过热灌注隔离肢体技术（HILP），可在肢体中实现高局部药物浓度，同时全身毒性最小。目前最成功的药物仍然是肿瘤坏死因子α（TNFα）和美法仑。作为肢体局部晚期原发性不可切除软组织肉瘤的诱导化疗治疗方法，HILP可实现71%的肢体挽救率，且治疗相关的发病率极低。HILP没有年龄上限。目前很少见到全身炎症反应综合征。TNFα的确切作用机制仍不清楚。目前实验工作致力于开发使肿瘤血管对TNFα作用敏感的药物。在临床HILP环境中，目前正在研究较低剂量的TNFα与美法仑联合使用。尽管多药耐药（MDR）是人类癌症化疗有效性的一个主要问题，但使用TNFα和美法仑的HILP并未在肉瘤中诱导产生MDR。未来针对TNFα的HILP研究方向是在不降低肿瘤反应的情况下，通过降低剂量来提高肿瘤对TNF的敏感性。
