title: Radioimmunotherapy for breast cancer using indium-111/yttrium-90 BrE-3: results of a phase I clinical trial.
abstract: BrE-3 is a murine IgG1 monoclonal antibody that binds to 97% of human ductal breast cancer specimens. A previous study documented the ability of 111In-labeled 1,4-methyl-benzyl isothiocyanate diethylenetriamine pentaacetic acid (111In-MX-DTPA) BrE-3 to specifically target breast cancer tissue in patients, and the dosimetry derived from the pharmacokinetics suggested that a useful therapeutic index could be obtained with 90Y-MX-DTPA BrE-3. A Phase I maximum tolerated dose study was, therefore, initiated.
  
  
  METHODS
  Six patients received 111In/90Y-MX-DTPA BrE-3, three of them receiving 6.25 and the other three receiving 9.25 mCi/m2 of 90Y. Pharmacokinetics, dosimetry, human anti-mouse antibody (HAMA), toxicity and clinical responses were evaluated.
  
  
  RESULTS
  Three of six patients demonstrated a minor and transient, but objective tumor response, and none of the patients had significant toxicity. Tumor dosimetry ranged from 39 to 167 rad/mCi of 90Y (442-1887 rad/ dose). HAMA response occurred in five of six patients.
  
  
  CONCLUSIONS
  Minimal toxicity, dosimetric calculations and clinical assessment indicate that a useful therapeutic index can be achieved with this therapy. Indium-111/yttrium-90-MX-DTPA BrE-3 can be safely administered to patients with metastatic breast cancer, and therapy doses yielded pharmacokinetics similar to those of tracer doses. Clinical responses, albeit transient, were achieved with single-dose therapy. Rapid onset of the HAMA response will hinder multicycle therapy, unless it is prevented with immunosuppressive drugs or the use of a "humanized" antibody. Further studies are needed to determine the optimal use of BrE-3 for radioimmunotherapy.
authors.affiliation: University of California at Davis, Sacramento, California, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: E L
authors.initials: EL
authors.lastname: Kramer
authors.forename: R T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: C M
authors.initials: CM
authors.lastname: Richman
authors.forename: Q A
authors.initials: QA
authors.lastname: Salako
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.forename: M
authors.initials: M
authors.lastname: Noz
authors.forename: S D
authors.initials: SD
authors.lastname: Glenn
authors.forename: R L
authors.initials: RL
authors.lastname: Ceriani
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D002614:Chelating Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D008875:Middle Aged; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D002614:Chelating Agents; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes; C077295:2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid; D004369:Pentetic Acid