title: Hyperthermic isolated limb perfusion with low-dose tumor necrosis factor-alpha and melphalan for bulky in-transit melanoma metastases.
abstract: BACKGROUND
  Melphalan (L-PAM) hyperthermic isolated limb perfusion (HILP) is currently considered the standard treatment for patients with in-transit metastases from cutaneous melanoma. We here report on the results of L-PAM and low-dose tumor necrosis factor (TNF)alpha HILP in patients with bulky disease.
  
  
  METHODS
  Twenty patients underwent TNFalpha (1 mg) and L-PAM (10 mg/L) HILP. Perfusion was performed for 90 minutes, and systemic leakage was strictly monitored. Locoregional toxicity was evaluated according to Wieberdink's criteria, whereas tumor response was evaluated with physical examination and ultrasound scan with or without fine-needle aspiration of any suspected recurrence.
  
  
  RESULTS
  In all cases, systemic leakage was <5%. No postoperative deaths occurred, and locoregional toxicity was mild (grade 1 or 2) in 95% of patients. A complete tumor response was obtained in 14 patients (70%), and partial responses were obtained in 5 patients (25%). After a median follow-up of 18 months, six patients are alive and disease free, seven are alive with local or distant recurrence or both, and seven have died of disease.
  
  
  CONCLUSIONS
  Low-dose TNFalpha HILP can achieve tumor responses comparable with those reported with higher doses of cytokine. Moreover, this drug regimen is associated with acceptable local toxicity, carries a smaller risk of systemic toxicity, and incurs lower costs.
authors.affiliation: Clinica Chirurgica Generale II, Dipartimento di Scienze Oncologiche e Chirurgiche, Università di Padova, Padova, Italy. carlor.rossi@unipd.it
authors.forename: Carlo Riccardo
authors.initials: CR
authors.lastname: Rossi
authors.forename: Mirto
authors.initials: M
authors.lastname: Foletto
authors.forename: Simone
authors.initials: S
authors.lastname: Mocellin
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pilati
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007558:Italy / Q000453:epidemiology; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan