title: High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.
abstract: OBJECTIVE
  A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA).
  
  
  METHODS
  After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria.
  
  
  RESULTS
  No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy.
  
  
  CONCLUSIONS
  Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.
authors.affiliation: Department of Internal Medicine, University of Nebraska, Medical Center, Omaha 68198-6805, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tempero
authors.forename: P
authors.initials: P
authors.lastname: Leichner
authors.forename: G
authors.initials: G
authors.lastname: Dalrymple
authors.forename: K
authors.initials: K
authors.lastname: Harrison
authors.forename: S
authors.initials: S
authors.lastname: Augustine
authors.forename: J
authors.initials: J
authors.lastname: Schlam
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Wisecarver
authors.forename: D
authors.initials: D
authors.lastname: Colcher
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007457:Iodine Radioisotopes; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; C091202:B72.3 antibody; D007457:Iodine Radioisotopes