title: Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma.
abstract: CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG-72 antigen. We carried out a Phase I study with escalating doses of 131I-CC49 in patients with advanced colorectal cancer expressing the TAG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate.
  
  
  METHODS
  Twenty-four patients with TAG-72- expressing colorectal cancer were treated with escalating doses of 131I-CC49 starting at 15 mCi/m2 and going up to 90 mCi/m2 of 131I labeled to 20 mg MAb CC49. Patients were selected if TAG-72 was expressed in > or = 50% of cells in previously resected tumor and at least one metastasis was demonstratable on standard imaging such as CT. All patients had failed conventional chemotherapy and had not received prior radiotherapy or murine MAb. Patients were under radiation isolation precautions until whole-body radioactivity decreased to < or = 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infusion in all patients. SPECT imaging was carried out at least once in all patients.
  
  
  RESULTS
  All patients had excellent targeting of radioactivity to known tumor sites. There was no nonhematologic toxicity. Hematologic toxicity was more pronounced in those patients who had received extensive prior chemotherapy. There were no major responses. All patients developed an immune response (HAMA) within 4 wk of therapy.
  
  
  CONCLUSIONS
  Radioimmunotherapy with 131I-CC49 is safe and there is significant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tumors. Dose-limiting toxicity is hematopoietic, with the maximum tolerated dose in this group of heavily pretreated patients being 75 mCi/m2.
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Divgi
authors.forename: A M
authors.initials: AM
authors.lastname: Scott
authors.forename: L
authors.initials: L
authors.lastname: Dantis
authors.forename: P
authors.initials: P
authors.lastname: Capitelli
authors.forename: K
authors.initials: K
authors.lastname: Siler
authors.forename: S
authors.initials: S
authors.lastname: Hilton
authors.forename: R D
authors.initials: RD
authors.lastname: Finn
authors.forename: N
authors.initials: N
authors.lastname: Kemeny
authors.forename: D
authors.initials: D
authors.lastname: Kelsen
authors.forename: L
authors.initials: L
authors.lastname: Kostakoglu
mesh_terms: D000008:Abdominal Neoplasms / Q000532:radiotherapy / Q000556:secondary; D000230:Adenocarcinoma / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000532:radiotherapy / Q000556:secondary; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007457:Iodine Radioisotopes; C047052:tumor-associated antigen 72