Randomized phase 2 study of bone‐targeted therapy containing strontium‐89 in advanced castrate‐sensitive prostate cancer

BACKGROUND Radiopharmaceutical use may improve the survival time of patients with castrate‐resistant prostate cancer and bone metastases. Whether androgen‐deprivation therapy (ADT) combined with bone‐targeted therapy provides a clinical benefit to patients with advanced castrate‐sensitive prostate cancer has not been investigated. METHODS Eighty male patients were enrolled, and 79 were randomized: 40 to the control arm and 39 to the strontium‐89 (Sr‐89) arm. After randomization, patients in both study arms received ADT, doxorubicin, and zoledronic acid. Kaplan‐Meier methodology was used to evaluate the progression‐free survival (PFS) time. Multivariate Cox proportional hazards regression was used to evaluate the effects of Sr‐89 after controlling for the number of bone metastases. RESULTS The median follow‐up time for the 29 patients alive at the last follow‐up was 76.9 months (range, 0.07‐103.4 months). The median PFS time was 18.5 months (95% confidence interval, 9.7‐49.4 months) for the control arm and 12.9 months (95% confidence interval, 8.9‐72.5 months) for the Sr‐89 arm (P = .86). No patient developed myelodysplastic syndrome or a hematologic malignancy. An unplanned subgroup analysis suggested increased efficacy of bone‐targeted therapy with a greater extent of bone involvement (ie, >6 bone metastases vs ≤6 bone metastases on the bone scan). CONCLUSIONS The data showed that bone‐targeted therapy using 1 dose of Sr‐89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate‐sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone‐targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation. Cancer 2015;121:69–76. © 2014 American Cancer Society. To the authors' knowledge, this is the first study that combines androgen‐deprivation therapy with a radiopharmaceutical agent for the treatment of patients with advanced castrate‐sensitive prostate cancer. Although an improvement in progression‐free survival has not been detected, the results suggest a favorable outcome for those patients with a greater tumor burden in the bone.