title: 20 years experience of TNF-based isolated limb perfusion for in-transit melanoma metastases: TNF dose matters.
abstract: 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.
authors: Department of Surgical Oncology, ErasmusMC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors: Jan P
authors: JP
authors: Deroose
authors: Alexander M M
authors: AM
authors: Eggermont
authors: Albertus N
authors: AN
authors: van Geel
authors: Johannes H W
authors: JH
authors: de Wilt
authors: Jacobus W A
authors: JW
authors: Burger
authors: Cornelis
authors: C
authors: Verhoef
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating