title: Long-term results of melphalan-based isolated limb perfusion with or without low-dose TNF for in-transit melanoma metastases.
abstract: BACKGROUND
  The aims of the study were: (1) to determine toxicity, response rate, local-regional control, and survival in the entire population of the perfused patients; (2) to compare toxicity, response, and survival among patients who underwent melphalan-based perfusion with or without low-dose tumor necrosis factor (TNF); and (3) to identify factors that predict a complete response and survival.
  
  
  METHODS
  A total of 53 patients with extensive in-transit metastases (47%) underwent perfusion with melphalan, and 59 (53%) also received low-dose TNF.
  
  
  RESULTS
  No difference was observed between the 2 drug regimens for what concerns local toxicity (P = 1.0). The tumor complete response rate was higher in patients treated with TNF (60.3% versus 41.5%, P = .036), in particular in the case of locally advanced tumors (66.7% versus 30%, P = .049). The presence of lymph node metastases had a negative influence on the tumor response rate (P = .003). Median time to local progression and survival were 19.6 and 34.5 months, respectively. Long-term complete response was achieved in 68% of the patients with initial CR (39 of 57 patients). The tumor response after perfusion was the only prognostic factor for local control and survival (P < .0001 and P = .002, respectively).
  
  
  CONCLUSIONS
  In the case of locally advanced disease, the addition of low-dose TNF to melphalan-based isolated limb perfusion appears safe and particularly useful. The presence of lymph node metastases is associated with decreased response rates. A sustained complete response was obtained in about one-third of the patients.
authors.affiliation: Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
authors.forename: Sandro
authors.initials: S
authors.lastname: Pasquali
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Antonella
authors.initials: A
authors.lastname: Vecchiato
authors.forename: Luca Giovanni
authors.initials: LG
authors.lastname: Campana
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pilati
authors.forename: Antonio
authors.initials: A
authors.lastname: Zanon
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan