The success of TNFα in isolated limb perfusion (ILP) in the management of locally advanced extremity tumors and future prospectives for isolated organ perfusions: Lesions from a clinical-preclinical interactive program

Tumor necrosis factor-α (TNFα) has been filed for registration in Europe for application in isolated limb perfusion for locally advanced extremity soft tissue sarcomas because of a high response rate of > 80% with a similarly successful limb salvage rate. TNF has also been shown to be active in the LP setting against other tumors, e.g., melanoma, osteosarcomas and various carcinomas. Therefore, the use of TNFα is now also explored for isolated organ perfusions such as isolated hepatic perfusion. At the Rotterdam Cancer Center a preclinical-clinical interactive program has been established dedicated to isolated limb, kidney, liver and lung perfusions and the application of new drugs such as TNF and TNF-mutants in these systems. Pharmacokinetics and the integration of new minimally invasive techniques such as using occlusion balloon catheters in hypoxic pelvic perfusions (HPP) and isolated hypoxic hepatic perfusions (IHHP) are investigated. Finally, the potential systemic application of TNF is investigated in tumor drug-targeting systems such as long-circulating liposomes. The potentially wide application of TNF, a drug that is in its 'second life', is discussed in this lecture.