title: Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.
abstract: OBJECTIVE
  To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma.
  
  
  METHODS
  Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status.
  
  
  RESULTS
  The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively).
  
  
  CONCLUSIONS
  In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Cornett
authors.forename: Linda M
authors.initials: LM
authors.lastname: McCall
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Petersen
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Henry A
authors.initials: HA
authors.lastname: Briele
authors.forename: R Dirk
authors.initials: RD
authors.lastname: Noyes
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sussman
authors.forename: William G
authors.initials: WG
authors.lastname: Kraybill
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: H Richard
authors.initials: HR
authors.lastname: Alexander
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Paul F
authors.initials: PF
authors.lastname: Mansfield
authors.forename: James F
authors.initials: JF
authors.lastname: Pingpank
authors.forename: David J
authors.initials: DJ
authors.lastname: Winchester
authors.forename: Richard L
authors.initials: RL
authors.lastname: White
authors.forename: Vijaya
authors.initials: V
authors.lastname: Chadaram
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Fraker
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods; D005121:Extremities; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D018579:Patient Selection; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D014481:United States
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan