Radioimmunotherapy for breast cancer using indium-111/yttrium-90 BrE-3: results of a phase I clinical trial

J Nucl Med. 1997 Aug;38(8):1180-5.

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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / radiotherapy*
  • Chelating Agents / therapeutic use
  • Female
  • Humans
  • Indium Radioisotopes / therapeutic use*
  • Middle Aged
  • Pentetic Acid / analogs & derivatives
  • Pentetic Acid / therapeutic use
  • Radioimmunotherapy*
  • Radiotherapy Dosage
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Chelating Agents
  • Indium Radioisotopes
  • Yttrium Radioisotopes
  • 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid
  • Pentetic Acid