4729 Background: Prostate carcinoma is linked to osteoblastic metastasis. We investigated the value of bone-targeted therapy in selected pts with AIPCa. Eligibility included progressive AIPCa affecting bone, presence of worsening cancer-related symptoms, increasing prostate-specific antigen (PSA) values on 2 occasions at least 2 weeks apart, castrate serum testosterone concentrations of < 50 ug/L, disease progression after antiandrogen withdrawal, life expectancy > 3 three months, Zubrod performance status of ≤ 2, and normal organ/marrow function. Methods: Each pt received strontium-89 at 4 mCi on week 1, day 1. Each course of chemotherapy lasted for 8 weeks. Pts were treated in weeks 1, 3, and 5 with doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on the 1st first day of every week) in combination with ketaconazole (400 mg orally 3 times a day daily for 7 days). In weeks 2, 4, and 6, treatment consisted of paclitaxel (100 mg/m2 intravenously on the first day of every week) in combination with estramustine (280 mg orally 3 times a day for 7 days). After completion of 2 courses of chemotherapy, patients with stable or responding disease completed 2 further courses. Pts were then placed on maintenance ketaconazole until their disease progressed. Results: 19 pts have enrolled. 13 pt have completed strontium-89 and 4 courses of chemotherapy. 6 pts are too early for evaluation. Based on a reduction in PSA concentrations of at least 50% from baseline maintained for at least 8 weeks, 9 pts responded to treatment. 1 pt had at least an 80% reduction in PSA concentrations. All pts with symptomatic bone pain reported that the pain improved during treatment. Toxic effects were assessed and included: 3 pts who developed deep venous thrombosis. 8 pts had grade 4 neutropenia. Severe thrombocytopenia grade ≥ 3 occurred in 6 pts.Other common side effects were; edema, fatigue, pain flare, nausea, vomiting, raised transaminases, and skin reaction. Conclusions: Bone-targeted therapy consisting of one dose of strontium-89 plus alternating chemotherapy demonstrated promising activity in pts with AIPCa with an acceptable tolerability. This program continues to enroll pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amersham