A phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases

BACKGROUND. The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma. METHODS. Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m² or 800 mg/m²) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 μCi/kg) was administered on Day 8. RESULTS. Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level I (gemcitabine 600 mg/m²) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m²). Platelet nadirs of 25,000-50,000 platelets per μL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per μL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease. CONCLUSIONS. The authors concluded that 800 mg/m² gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted.