title: Phase I study of 131I-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer.
abstract: OBJECTIVE
  The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues.
  
  
  METHODS
  Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg).
  
  
  RESULTS
  The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses.
  
  
  CONCLUSIONS
  The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA 943053, USA.
authors.forename: Hilary Hardy
authors.initials: HH
authors.lastname: Street
authors.forename: Michael L
authors.initials: ML
authors.lastname: Goris
authors.forename: George Albert
authors.initials: GA
authors.lastname: Fisher
authors.forename: Barry W
authors.initials: BW
authors.lastname: Wessels
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cho
authors.forename: Carmen
authors.initials: C
authors.lastname: Hernandez
authors.forename: Hongyun June
authors.initials: HJ
authors.lastname: Zhu
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jasvinder Singh
authors.initials: JS
authors.lastname: Nangiana
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Shan
authors.forename: Karen
authors.initials: K
authors.lastname: Roberts
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D015179:Colorectal Neoplasms / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D016499:Radioimmunotherapy / Q000295:instrumentation* / Q000379:methods*; D011874:Radiometry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha