First clinical experience with α-emitting radium-223 in the treatment of skeletal metastases

Purpose: The main goals were to study the safety and tolerability of the alpha-emitter radium-223 (Ra-223) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated. Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of Ra-223. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks, Palliative response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1, 4, and 8 weeks after injection. Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection. Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. Ra-223 cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance with pretreatment Tc-99m-MDP scans, accumulation of Ra-223 in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months. Conclusions : Ra-223 was well tolerated at therapeutically relevant dosages. Phase 11 studies have therefore been initiated.