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

Cancer. 2015 Jan 1;121(1):69-76. doi: 10.1002/cncr.28971. Epub 2014 Aug 22.

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.

Keywords: bone metastasis; phase 2; prostate cancer; radiopharmaceutical; strontium-89.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy*
  • Combined Modality Therapy / methods
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use
  • Male
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Strontium Radioisotopes / administration & dosage*
  • Strontium Radioisotopes / therapeutic use
  • Survival Analysis
  • Treatment Outcome
  • Zoledronic Acid

Substances

  • Antineoplastic Agents, Hormonal
  • Diphosphonates
  • Imidazoles
  • Strontium Radioisotopes
  • Zoledronic Acid
  • Doxorubicin