Effects of radium-223 (Ra-223) with docetaxel versus docetaxel alone on bone biomarkers in patients with bone-metastatic castration-resistant prostate cancer (CRPC): A phase I/IIa clinical trial.

154Background: Interactions between metastatic prostate cancer cells, osteoblasts, osteoclasts, and other participants in bone metabolism are complex and result in pathologic bone physiology. Ra-223, a targeted alpha therapy, accumulates at sites of bone metastases and prolongs survival. Ra-223 and docetaxel (D), acting through different mechanisms of action, may have beneficial effects on bone pathophysiology and tumor microenvironment. Prior data suggest treatment with Ra-223 results in favorable alterations in bone biomarkers that are associated with survival. Methods: 53 patients with progressing CRPC and ≥ 2 bone metastases were randomized 2:1 to Ra-223 (55 kBq/kg q6wk × 5) + D (60 mg/m2 q3wk × 10) versus D (75 mg/m2 q3wk with step-down option to 60 mg/m2). Bone resorption (CTX-1, ICTP) and formation (P1NP, bALP) markers, tALP, and PSA were analyzed at wk 19 (after 3 Ra-223 injections) and 3 wk after end of treatment (EOT). Results: Mean % change at wk 19 and EOT are shown (Table). tALP, bALP, P1NP, ...