Prognostic role of serum parathyroid hormone levels in advanced prostate cancer patients undergoing zoledronic acid administration

Oncologist. 2012;17(5):645-52. doi: 10.1634/theoncologist.2011-0448. Epub 2012 Apr 20.

Abstract

Background: Secondary hyperparathyroidism is frequent in prostate cancer patients with bone metastases, and this condition is worsened by the administration of potent bisphosphonates. Serum parathyroid hormone (PTH) elevation can impair the efficacy of these drugs in terms of survival.

Methods: The prognostic role of elevated serum PTH levels at baseline and after 3 months of zoledronic acid administration was assessed prospectively in 643 bone metastatic prostate cancer patients enrolled in a prospective randomized, placebo-controlled study.

Results: On multivariate analysis, after adjusting for major prognostic factors and bone turnover markers, elevated baseline serum PTH level was negatively associated with overall survival (hazard ratio [HR], 1.448; 95% confidence interval [CI], 1.045-2.006; p < .03) in zoledronic acid-treated patients but not in placebo-treated patients. In patients with normal baseline PTH levels, there was a trend but insignificant association between zoledronic acid administration and a better survival outcome than with placebo (HR, 0.81; 95% CI, 0.65-1.01; p = .065), whereas a trend in the opposite direction was observed in patients with elevated PTH levels (HR, 1.45; 95% CI, 0.87-2.39; p = .151); interaction test, p = .040. Elevated serum PTH level after 3 months of zoledronic acid treatment was not significantly associated with survival outcome.

Conclusions: Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / blood*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Disease Progression
  • Double-Blind Method
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / chemically induced
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Parathyroid Hormone / blood*
  • Prognosis
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy*
  • Survival Analysis
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Parathyroid Hormone
  • Zoledronic Acid