Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody

A Phase I dose-escalation study using ⁹⁰Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using ¹¹¹In-CYT-356 were performed 1 week before ⁹⁰Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of ¹¹¹In-CYT-356. The dose of ⁹⁰Y ranged from 1.83-12 mCi/m². Both ¹¹¹In and ⁹⁰Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m². Of the patients receiving ≤9 mCi/m², 55% had grade 1 or 2 leukopenia and/or thrombocytopenia. Two of three patients treated with 12 mCi/m² experienced grade 3 thrombocytopenia and leukopenia. One patient treated with 12 mCi/m² had grade 4 neutropenia. The maximum tolerated dose of ⁹⁰Y-CYT-356 was 9 mCi/m². Only one patient developed a human anti-mouse antibody 4 weeks after treatment. No patient attained a complete or partial response based on prostate-specific antigen and/or radiological criteria. Three patients had transient subjective improvement in the symptomatology of their disease. In addition, patients treated with 12 mCi/m² of ⁹⁰Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of ⁹⁰Y-CYT-356 ≤9 mCi/m².