title: Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.
abstract: BACKGROUND
  Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation.
  
  
  METHODS
  From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature).
  
  
  RESULTS
  Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6).
  
  
  CONCLUSIONS
  The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.
authors.affiliation: Department of Surgical Oncology B, National Cancer Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vaglini
authors.forename: F
authors.initials: F
authors.lastname: Belli
authors.forename: M
authors.initials: M
authors.lastname: Ammatuna
authors.forename: M G
authors.initials: MG
authors.lastname: Inglese
authors.forename: R
authors.initials: R
authors.lastname: Manzi
authors.forename: A
authors.initials: A
authors.lastname: Prada
authors.forename: L
authors.initials: L
authors.lastname: Persiani
authors.forename: M
authors.initials: M
authors.lastname: Santinami
authors.forename: N
authors.initials: N
authors.lastname: Santoro
authors.forename: N
authors.initials: N
authors.lastname: Cascinelli
mesh_terms: D000328:Adult; D000368:Aged; D001132:Arm; D002277:Carcinoma / Q000188:drug therapy; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D012509:Sarcoma / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan