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Knox SJ , Goris ML , Tempero M , Weiden PL , Gentner L , Breitz H , Adams GP , Axworthy D , Gaffigan S , Bryan K , Fisher DR , Colcher D , Horak ID , Weiner LM
Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU- 10 antibody/streptavidin in patients with metastatic colon cancer
Clinical Cancer Research. 2000 Feb;6(2) :406-414
PMID: ISI:000085502600013   
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Abstract
A Phase II study of yttrium-90-tetra-azacyclododecanetetra- acetic acid-biotin (Y-90-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients,were treated with a single dose of 110 mCi/m(2) (mean administered 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 administered similar to 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin- DOTA-labeled with 110 mCi/m(2) Y-90. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed, Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity 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. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new. information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs.
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Times Cited: 24 English Article 287JK CLIN CANCER RES