title: [Isolated hyperthermic limb perfusion with melphalan and tumor necrosis factor in malignant melanoma].
abstract: OBJECTIVE
  To analyse a personal series of cases of malignant melanoma of a limb with regional metastasis treated by isolated cytostatic perfusion of both recombinant human tumour necrosis factor (rhTNF-alpha) and melphalan, reported to produce a response rate of up to 100%.
  
  
  METHODS
  23 isolated hyperthermic regional perfusions were performed between 1993 and 1995 in 21 patients (17 women, four men) with proven regionally metastatic malignant melanoma of the limb, using rhTNF-alpha and melphalan in combination. Perfusion time was 90 min, at a tissue temperature of 38 degrees to 40 degrees C and a perfusion pressure 10-15 mm Hg below mean arterial.
  
  
  RESULTS
  All systemic effects of the limb perfusions were easily manageable under intensive care monitoring. There were no severe disturbances (WHO grade 3/4) of cardiovascular or pulmonary functions. One patient, who had sustained a marked leak during the perfusion, died two days after the perfusion of severe pneumonia and pulmonary emboli from a femoral vein thrombosis. Two further perfusions were terminated because of a leakage rate of more than 10%. A rise in bilirubin and the transaminases occurred in 11 of the 23 perfusions up to WHO grade 2 (n = 9) and 3 (n = 2). Renal functions were temporarily impaired in three of the 21 patients (WHO grade 1). Complete tumour regression was obtained in 13 patients, a partial one in three (response rate 80%). After a median follow-up period of 15 months five of the 13 patients developed a regional recurrence.
  
  
  CONCLUSIONS
  The observed response rate is higher than that with melphalan alone as reported in the literature. To clarify this difference a randomized phase III study comparing the two methods has been initiated.
authors.affiliation: Abteilung für Chirurgie und Chirurgische Onkologie, Robert-Rössle-Klinik am Max-Delbrück-Centrum für Molekulare Medizin, Virchow-Klinikum der Humboldt-Universität zu Berlin.
authors.forename: C
authors.initials: C
authors.lastname: Kettelhack
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.forename: P M
authors.initials: PM
authors.lastname: Schlag
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan
vernacular_title: Die isolierte hypertherme Extremitätenperfusion beim malignen Melanom mit Melphalan und Tumornekrosefaktor.