title: Hyperthermic pelvic perfusion with tumor necrosis factor-α for locally advanced cancers: encouraging results of a phase II study.
abstract: OBJECTIVE
  To assess the efficacy of isolated pelvic perfusion (IPP) with tumor necrosis factor (TNF)-α and melphalan in patients with locally advanced cancers in the pelvic and groin area requiring mutilating surgery.
  
  
  METHODS
  A total of 27 patients were enrolled (carcinoma, n = 17; sarcoma/melanoma, n = 4; and endocrine tumor, n = 6). They were candidates for exarticulation (n = 3) or exenteration (n = 11) or were judged unresectable (n = 13). In installing IPP, tourniquets were positioned around both thighs, and an inflated pressure suit was placed at a subthoracic position. Tumor necrosis factor-α (300 μg) was injected in the perfusate, followed 5 minutes later by melphalan at 1.5 mg/kg. After 30 minutes, the remaining drugs were washed out. Leakage was assessed with technetium Tc 99m radiolabeled human serum albumin, and a pharmacokinetic study was performed. Efficacy was based on the complete response rate observed on magnetic resonance imaging.
  
  
  RESULTS
  Pelvic/systemic ratios of melphalan/TNF/technetium Tc 99m were 14.2/7/3.6. Responses on magnetic resonance imaging were as follows: 30% complete, 30% partial, 19% no change, and 15% progression. Two patients were not evaluable because they did not receive the treatment. Pre-IPP/post-IPP median percentage of necrosis on magnetic resonance imaging was 10%/70%. Median follow-up was 43 months. Median overall survival was 17 months. Twelve-month survival rate, disease-free survival, and local and metastatic recurrence rates were 67%, 30%, 57%, and 26%, respectively.
  
  
  CONCLUSIONS
  Isolated pelvic perfusion with TNF-α compares favorably with historical data, as it was observed in limb perfusion and could provide a chance to translate its successful combination with chemotherapy into treatment of locally advanced pelvic cancers.
authors.affiliation: Department of Surgery, Institut Gustave-Roussy, Villejuif Cedex, France. bonvalot@igr.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bonvalot
authors.forename: Thierry
authors.initials: T
authors.lastname: de Baere
authors.forename: Jean
authors.initials: J
authors.lastname: Mendiboure
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Françoise
authors.initials: F
authors.lastname: Farace
authors.forename: Laurence
authors.initials: L
authors.lastname: Drouard-Troalen
authors.forename: Laure
authors.initials: L
authors.lastname: Bonnet
authors.forename: Antoine
authors.initials: A
authors.lastname: Hakime
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bonniaud
authors.forename: Bruno
authors.initials: B
authors.lastname: Raynard
authors.forename: Philippe
authors.initials: P
authors.lastname: Israel
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Agnès
authors.initials: A
authors.lastname: Laplanche
authors.forename: Jane
authors.initials: J
authors.lastname: Muret
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D018572:Disease-Free Survival; D004701:Endocrine Gland Neoplasms / Q000188:drug therapy / Q000401:mortality; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D010386:Pelvic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012509:Sarcoma / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan