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

Abstract

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/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/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 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL 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/m(2) 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. .