title: Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer.
abstract: 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.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mehmet Asim
authors.initials: MA
authors.lastname: Bilen
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Paul
authors.initials: P
authors.lastname: Mathew
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: John C
authors.initials: JC
authors.lastname: Araujo
authors.forename: Ana
authors.initials: A
authors.lastname: Aparicio
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.forename: Franklin C
authors.initials: FC
authors.lastname: Wong
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisch
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Tu
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013326:Strontium Radioisotopes / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004164:Diphosphonates; D007093:Imidazoles; D013326:Strontium Radioisotopes; D000077211:Zoledronic Acid; D004317:Doxorubicin
keywords: bone metastasis; phase 2; prostate cancer; radiopharmaceutical; strontium-89