title: Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma.
abstract: Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: L M
authors.initials: LM
authors.lastname: Minasian
authors.forename: T P
authors.initials: TP
authors.lastname: Szatrowski
authors.forename: M
authors.initials: M
authors.lastname: Rosenblum
authors.forename: T
authors.initials: T
authors.lastname: Steffens
authors.forename: M E
authors.initials: ME
authors.lastname: Morrison
authors.forename: P B
authors.initials: PB
authors.lastname: Chapman
authors.forename: L
authors.initials: L
authors.lastname: Williams
authors.forename: C F
authors.initials: CF
authors.lastname: Nathan
authors.forename: A N
authors.initials: AN
authors.lastname: Houghton
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015275:Tumor Lysis Syndrome / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D005732:Gangliosides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; C026226:ganglioside, GD3; D013755:Tetradecanoylphorbol Acetate