title: Phase I/II trial of (131)I-MN-14F(ab)2 anti-carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma.
abstract: BACKGROUND
  Monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) have been recognized as targeting agents for medullary thyroid carcinoma (MTC). This Phase I/II study was initiated to determine the safety, maximum tolerated dose (MTD), and therapeutic potential of (131)I-MN-14 F(ab)2 anti-CEA MAb for patients with metastatic MTC.
  
  
  METHODS
  Fifteen patients were enrolled in this study. Dose escalation was based on estimates of radiation dose to the bone marrow, and the radioactive dose given was determined by a pretherapy diagnostic study in which 8 mCi (0.6-20 mg) of (131)I-MN-14 F(ab)2 was administered 1 week prior to therapy.
  
  
  RESULTS
  Three patients received an initial dose of 140 centigray (cGy) to bone marrow, 11 received 180 cGy, and 1 received 220 cGy. Myelosuppression was the only significant treatment-related dose-limiting toxicity (DLT), and the MTD appeared to be 180 cGy to the bone marrow. Human antimouse antibodies (HAMA) developed in 8 patients 2-6 weeks after therapy. Seven patients had a median of 55% reduction of tumor markers. One patient showed a dramatic improvement in the mass effect on the airways caused by 3 tumor lesions in the neck, with a 45% reduction of overall tumor burden. The disease has continued to be radiologically stable in 11 of 12 assessable patients for periods ranging from 3+ to 26+ months.
  
  
  CONCLUSIONS
  Therapy with (131)I-MN-14 F(ab)2 is well tolerated and shows evidence of biochemical and radiologic antitumor activity. HAMA development suggests that humanized MAbs will be required in trials with repeated dose schedules. Further dose escalation, alone or in combination with other therapy modalities, is indicated for future trials, preferably with humanized anti-CEA MAbs.
authors.affiliation: Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Juweid
authors.forename: G
authors.initials: G
authors.lastname: Hajjar
authors.forename: L C
authors.initials: LC
authors.lastname: Swayne
authors.forename: R M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: S
authors.initials: S
authors.lastname: Suleiman
authors.forename: T
authors.initials: T
authors.lastname: Herskovic
authors.forename: M
authors.initials: M
authors.lastname: Pereira
authors.forename: A D
authors.initials: AD
authors.lastname: Rubin
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002116:Calcitonin / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D018276:Carcinoma, Medullary / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy* / Q000556:secondary* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008875:Middle Aged; D037981:Neck Dissection; D009363:Neoplasm Proteins / Q000097:blood; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013965:Thyroidectomy; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D002116:Calcitonin; C110010:labetuzumab