Radium-223 Dichloride–Associated Toxicity in Post-Chemotherapy Patients with Castration-Resistant Prostate Cancer and Bone Metastases

Background: Radiation pharmacokinetics and pharmacodynamics of Radium point to bone as its site of primary uptake and action. It is therefore very important to investigate the hematological and other toxicity of the radiopharmaceutical Radium -223 dichloride in the wake of its introduction for treatment of bone metastases. Methods: Five Patients with post-chemotherapy castrate resistant prostate cancer with bone metastases received 50kBq/ kg body weight of Radium-223 Dichloride injection every 4 weeks for 5 cycles. 1. Screening 2. Treatment (including an End of Treatment Visit) 3. Follow-up Results: The ranges of measured parameters for 4 patients at the end of 5th cycle (20th week) were within normal limits: Hb : Wk 20 = 110 -126g/l, pre-treatment = 110-136g/l (normal range 120-170) Wbc: Wk 20 = 3.3-6.2x109/l, Pre-treatment=3.5-8.9x109/l (normal range 4.5-10) Platelets: Wk 20 = 156-241x109/l, pre-treatment = 206-302x109/l (normal range 150-400). Alkaline Phosphatase: Wk 20 = 43-128IU/l, Pre-treatment = 57-253IU/l (normal Range 40-120). The 5th Patient developed bone marrow failure in the 12th week, with concurrent flaring of his alkaline phosphatase value. Conclusion: The results of this study suggest that Radium-223 dichloride at dose of 50kbq/kg is safe for palliative treatment of bone pains in metastatic bone diseases. The 5th patient’s bone marrow failure cause may be attributed to several factors such as 1. Direct effect of the drug on bone tissues 2. Drug induced allergic response 3. myelosuppression worsened by concomitant radiotherapy.