2554 Background: While RIT alone is effective in lymphoma, its application to more radioresistant solid tumors will likely require a combined approach similar to the use of radiosensitizing chemotherapy with external beam radiotherapy. Methods: Patients with metastatic hormone-refractory PC or advanced BC were imaged with Indium-111-DOTA-peptide-m170 (In-111-m170). One week later, Y-90-m170 was infused (12mCi/m2 for PC, 22mCi/m2 for BC). Initial cohorts received RIT alone. Subsequent cohorts received RIT followed by PT (75 mg/m2) 48 hours after RIT, a time when most radioactivity is concentrated in tumor and has been eliminated from normal tissues. Cyclosporin A (CSA) was given to prevent development of human antimouse antibody (HAMA). Peripheral blood stem cells (PBSC) were harvested prior to imaging for BC patients. Results: Bone and soft tissue metastases were targeted by In-111-m170 in 15 of the 16 patients imaged, with no unexpected uptake in normal tissue. 13 patients were treated with Y-90-m170. In 3 PC patients treated with RIT alone, no Grade 3/4 toxicity was seen. With RIT plus PT, 2 of 3 PC patients had neutrophils (ANC)<500/uL. In BC, with RIT alone, 1 of 4 patients had ANC <500, and 2 had platelets (pl) <25K. With RIT plus PT, all 3 BC patients had ANC < 500 and 2 of 3 had pl<25K. PBSC were given to 3 BC patients because of neutropenic fever or bleeding. One patient developed + HAMA (6%) in contrast to 71% of patients in a prior trial using m170 without CSA. Conclusions: Y-90-m170 targeted PC and BC. In combination with PT, toxicity was limited to marrow suppression at the dose levels above. Myelosuppression can be ameliorated by PBSC, and the maximum tolerated dose of RIT plus fixed-dose PT with PBSC support has not been reached. CSA was effective in preventing HAMA, suggesting the possibility of repeated “fractionated” therapy that could enhance antitumor response. No significant financial relationships to disclose.