Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer

A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biot in (Y-90-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) wa s performed. The primary objectives of the study were to evaluate the effic acy and safety of this therapy in patients with metastatic colon cancer. Tw enty-five patients,were treated with a single dose of 110 mCi/m(2) (mean ad ministered dose, 106.5 +/- 10.3 mCi/m(2)) of Y-90- DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administere d similar to 48 h after the NR-LU-10/SA to remove residual circulating unbo und NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patie nts received biotin-DOTA-labeled with 110 mCi/m(2) Y-90. All three componen ts of the therapy were administered i.v. Both hematological and nonhematolo gical toxicities were observed, Diarrhea was the most frequent grade 4 nonh ematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxic ity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 1 thrombocytopenia. The overall response rate nas 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20,weeks. Desp ite the relatively disappointing results of this study in terms of therapeu tic efficacy and toxicity, proof of principle was obtained for the pretarge ting approach. In addition, valuable new. information was obtained about no rmal tissue tolerance to low-dose-rate irradiation that will help to provid e useful guidelines for future study designs.