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: Mehmet Asim Bilen, Marcella M Johnson, Paul Mathew, Lance C Pagliaro, John C Araujo, Ana Aparicio, Paul G Corn, Nizar M Tannir, Franklin C Wong, Michael J Fisch, Christopher J Logothetis, Shi-Ming Tu
• Journal: Cancer (Cancer) Vol. 121 Issue 1 Pg. 69-76 (Jan 01 2015) ISSN: 1097-0142 [Electronic] United States
• PMID: 25155428 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2014 American Cancer Society.

Chemical References

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

Topics

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