20 years experience of TNF-based isolated limb perfusion for in-transit melanoma metastases: TNF dose matters

Ann Surg Oncol. 2012 Feb;19(2):627-35. doi: 10.1245/s10434-011-2030-7. Epub 2011 Aug 31.


Background: Approximately 5-8% of melanoma patients will develop in-transit metastases (IT-mets). Tumor necrosis factor-α (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is an attractive treatment modality in melanoma patients with multiple IT-mets. This study reports on a 20 years experience and outlines the evolution and major changes since the introduction of TNF in ILP.

Methods: A total of 167 TM-ILPs were performed in 148 patients, between 1991 and 2009. TM-ILPs were performed at high doses of TNF (3-4 mg) from 1991 to 2004 (n = 99) and at low doses of TNF (1-2 mg) from 2004 to 2009 (n = 68) under mild hyperthermic conditions (38°C-39.5°C.). Melphalan doses were unchanged at 10-13 mg/l (leg and arm, respectively). Characteristics for the 167 ILPs were: 81 stage IIIB, 65 stage IIIC, and 21 stage IV disease.

Results: The overall response rate was 89% (n = 148). (Complete response [CR] = 61%; partial response [PR] = 28%). CR rates correlated with stage (P = .001) and with high-dose vs. low-dose TNF (70% vs. 49%; P < .006). High-dose TNF prolonged local control (median 16 months vs. 11 months; P = .076). Survival was not influenced by TNF dose. CR after ILP and number of lesions also correlated with local progression-free interval. Overall survival did correlate with stage of disease (P < .001), size of the lesions (P = .001), and a CR (P < .001).

Conclusions: This 2-decade single-center experience demonstrates that TM-ILP is a safe and effective treatment modality for melanoma patients with multiple IT-mets. Higher dose of TNF was associated with significantly higher CR rates and prolonged local control without an effect on overall survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Chemotherapy, Cancer, Regional Perfusion*
  • Female
  • Follow-Up Studies
  • Humans
  • Leg*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality*
  • Middle Aged
  • Neoplasm Staging
  • Remission Induction
  • Survival Rate
  • Time Factors
  • Treatment Outcome


  • Antineoplastic Agents, Alkylating