Aims: Isolated limb perfusion with TNF and melphalan (TM-ILP) is highly effective in the local treatment of advanced sarcoma and melanoma of the limb. The optimal dose of TNF for this procedure is not well established. The aim of this study was to assess the efficacy and toxicity of TM-ILPs with reduced TNF dose. Method: Largest single institution prospective database on TNF-based ILP. Out of 339 TM-ILPs performed between 1991 and 2003, 64 procedures were performed with reduced TNF dose (<3 mg in arm perfusions, <4 mg in leg perfusions). Response rates and toxicity of the procedure and outcome of the patients are evaluated. Results: Complete response in melanoma patients after reduced-dose ILP was 75 vs 69% after standard-dose ILPs (overall response 94 vs 95%, respectively); overall response in non-melanoma patients was 69 (reduced) vs 74% (standard). Response rates and outcome were comparable with the procedures performed with standard-dose TNF (p=NS for response, local/systemic progression and survival after multivariate analysis, both in melanoma and in non-melanoma patients). Systemic and local toxicity did not differ statistically between reduced- and standard dose TM-ILPs. Conclusion: Provided doses at 1 mg or higher are used, TM-ILP with TNF dose reduction for both melanoma and non-melanoma patients seems to be as effective as the standard dose procedure in terms of response rate and patient outcome. Numbers to formally confirm or reject this hypothesis are too large for such a non-inferiority trial to be conducted in patients with these rare conditions.

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Keywords Isolated limb perfusion, Limb salvage, Melanoma, Melphalan, Soft tissue sarcoma, TNF
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Journal European Journal of Surgical Oncology
Grünhagen, D.J, de Wilt, J.H.W, van Geel, A.N, Graveland, W.J, Verhoef, C, & Eggermont, A.M.M. (2005). TNF dose reduction in isolated limb perfusion. European Journal of Surgical Oncology, 31(9), 1011–1019. doi:10.1016/j.ejso.2005.07.003