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

Abstract

UNLABELLED:

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.

• Authors: S J DeNardo, E L Kramer, R T O'Donnell, C M Richman, Q A Salako, S Shen, M Noz, S D Glenn, R L Ceriani, G L DeNardo
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 38 Issue 8 Pg. 1180-5 (Aug 1997) ISSN: 0161-5505 [Print] United States
• PMID: 9255145 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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