Systemic radiotherapy in metastatic breast cancer using Y-90-linked monoclonal MUC-1 antibodies

Radioimmunotherapy (RIT) is a promising approach for treating metastatic br east cancer. Initial clinical trials using I-131 radioimmunoconjugates, and more recent studies employing Y-90. have demonstrated objective, although transient, antitumor effects in heavily pretreated patients with minimal to xicity. Antibodies targeting unique epitopes of epithelial glycoprotein muc in(MUC-I) on breast cancer cell surfaces that have been studied in patients include BrE-3 (murine and humanized) and m170 (murine). Both antibodies re act with at least 90% of breast cancers. In these and other RIT trials, mye losuppression has been the dose-limiting toxicity. However, this toxicity h as been successfully circumvented with the use of autologous peripheral blo od stem cell transplantation. and recent clinical trials have escalated Y-9 0 doses up to 50 mCi/m(2). The therapeutic index indicates that using these agents with stem cell support should deliver 9000 to 18 000 rads to metast atic tumors. Development of improved chelates that are readily metabolized in the liver may reduce doses to this organ, projected to be next in line a s dose-limiting. Combination therapy will be required to produce durable be nefits in metastatic breast cancer. Low dose taxanes are synergistic with R IT in preclinical studies and when administered in the optimal sequence cou ld sensitize tumor cells to the continuous low dose radiation delivered by RIT, without increasing toxicity. The addition of systemically administered tumor targeting radiation therapy using RIT as part of combined modality t herapy may enhance the rate of complete response and, in patients with mini mal metastatic disease. could lead to curative therapy. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.