Hyperthermic isolated limb perfusion in the management of extremity sarcoma.
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.
Hoekstra
H J
HJ
Division of Surgical Oncology, Department of Surgery, Groningen University Hospital, PO Box 30.001, 9700 RB Groningen, The Netherlands. h.j.hoekstra@chir.azg.nl
van Ginkel
R J
RJ
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D006801:Humans; D006979:Hyperthermia, Induced; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D012509:Sarcoma / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan