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Radioimmunotherapy for Breast Cancer Using Indium-lll/Yttrium-90 BrE-3: Results of a Phase I Clinical Trial

University of California at Davis, Sacramento, California
New York University, New York, New York
Coulter Immunology, Hialeah, Florida
Cancer Research Fund of Contra Costa, Walnut Creek, California
Veterans Administration Northern California Health Care System, California

Correspondence: For correspondence or reprints: S. J. DeNardo, MD, Molecular Cancer Institute, 1508 Alhambra Boulevard, No. 214, Sacramento, CA 95816.

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 ¹¹¹n-labeled 1, 4-methyl-benzyl isothiocyanate diethylenetriamine pentaacetic acid (¹¹¹n-MX-DTPA)BrE-3 to specifically target breast cancer tissue in patients, and the dosimetry derived from the pharmacokinetics suggested that a useful thera peutic 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. Conclusion: Minimal toxicity,dosimetrie 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.

Key Words: breast cancer • radioimmunotherapy • BrE-3 • yttrium-90

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