Hyperthermic isolated limb perfusion in the management of extremity sarcoma

&NA; 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 (TNF&agr;) 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 TNF&agr; are still unknown. Experimental work is now directed to the development of drugs sensitizing the tumor vasculature to the effects of TNF&agr;. In the clinical HILP setting are currently lower doses of TNF&agr; in combination with melphalan investigated. Although multidrug resistance (MDR) is a major issue in effectiveness of chemotherapy in human cancer treatment, HILPs with TNF&agr; and melphalan did not induce MDR in sarcomas. The future research in HILP with TNF&agr; is directed in increasing tumor sensitivity for TNF with lowering the dosage without decreasing tumor response.

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