Radioimmunotherapy for breast cancer using indium-11 l/yttrium-90 BrE-3: Results of a phase i clinical trial

Academic Article

Abstract

  • BrE-3 is a murine \gG-4 monoclonal antibody that binds to 97% of human ductal breast cancer specimens. A previous study documented the ability of1111n-labeled 1,4-methyl-benzyl isothiocyanate diethylenetriamine pentaacetic acid (1111n-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 -4In/-4Y-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 radioirnmunotherapy.
  • Authors

    Published In

    Author List

  • Denardo SJ; Kramer EL; O'Donnell RT; Richman CM; Salako QA; Shen S; Noz M; Glenn SD; Ceriani RL; Denardo GL
  • Start Page

  • 1180
  • End Page

  • 1185
  • Volume

  • 38
  • Issue

  • 8