TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature

Br J Cancer. 2015 Aug 11;113(4):645-52. doi: 10.1038/bjc.2015.246. Epub 2015 Jul 14.


Background: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation.

Methods: A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues.

Results: Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure.

Conclusion: No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Cancer, Regional Perfusion / methods
  • Extremities / pathology*
  • Hemoglobins / metabolism
  • Humans
  • Hyperthermia, Induced / methods
  • Melphalan / administration & dosage
  • Middle Aged
  • Muscles / drug effects
  • Muscles / metabolism
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Oxygen / metabolism
  • Regional Blood Flow / drug effects*
  • Tumor Necrosis Factor-alpha / administration & dosage


  • Antineoplastic Agents, Alkylating
  • Hemoglobins
  • Tumor Necrosis Factor-alpha
  • Melphalan
  • Oxygen