Radium-223 chloride, a first-in-class alpha-pharmaceutical for patients with castration-resistant prostate cancer (CRPC) and bone metastases: Biodistribution/dosimetry compared to overall safety profile.

Abstract

e15009 Background: Radium-223 chloride (Alpharadin) is a first-in-class targeted alpha-pharmaceutical with a potent and highly targeted antitumor effect on bone metastases. It has shown a promising survival benefit, a benign safety profile and pain improvement in patients (pts) with bone metastatic CRPC. Biodistribution/dosimetry was evaluated in the context of safety. Methods: 6 pts with bone-metastatic CRPC received 2 radium-223 doses, 100 kBq/kg, 6 weeks apart. Blood, urine and feces were collected before and at regular intervals after injection. Whole body gamma camera imaging determined biodistribution. Radiation dose was calculated with adjustments for GI tract, heart wall, red marrow (RM) and osteogenic cells (OC). It was also taken into consideration that the product emits short range, high energy alpha particles. Overall safety and tolerability were evaluated in 292 pts across all Phase I/II trials. Results: Radium-223 wasrapidly eliminated from blood and taken up in bone (∼60% at 4hr) or excreted into the small intestine. There was <5% urinary and no hepato-biliary excretion. Highest calculated absorbed doses were to OC, RM and lower large intestine wall. In separate studies of 292 pts who had received range administered activities, <1% had CTC grade 4 hematological toxicity, 2-4% had grade 3 toxicity for HB, platelets, neutrophils, WBC. Mainly mild to moderate and reversible AEs were seen in the GI tract. Conclusions: Radium-223 was rapidly sequestered to bone/bone metastases and excreted in the GI tract. Due to the very short range of alpha particles (2-10 cell diameters), only a small volume of RM would have received a significant radiation dose, possibly accounting for the favorable hematologic safety profile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Algeta ASA Algeta ASA Algeta ASA