How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-analysis of randomized trials

Crit Rev Oncol Hematol. 2019 Oct:142:68-75. doi: 10.1016/j.critrevonc.2019.07.013. Epub 2019 Jul 25.

Abstract

Background: Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. Some randomized trials supported its role also when administered every 12 weeks.

Methods: we performed a systematic review and a meta-analysis in order to evaluate the two different schedules in terms of skeletal morbidity rate (SMR), skeletal related events (SRE) and adverse events (AEs).

Results: our results showed a clinical difference favouring the 12-week schedule in terms of AEs (RR 1.17, 95% CI 1.06-1.29). No signifcant differences were found for SMR (RR 0.97, 95% CI 0.84-1.13) and SRE (RR 1.02, 95% CI 0.89-1.16).

Conclusions: Our findings support in clinical practice the 12-week schedule an alternative to the standard 4-week schedule in advanced breast and prostate cancer, in particular when the clinical comorbidities of the patients suggest a higher risk of renal failure or hypocalcaemia.

Keywords: AEs; Bone metastases; Breast; Meta-Analysis; Prostate; SMR; Solid tumors; Zoledronic acid.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Prostatic Neoplasms / pathology
  • Treatment Outcome
  • Zoledronic Acid / administration & dosage
  • Zoledronic Acid / adverse effects
  • Zoledronic Acid / therapeutic use*

Substances

  • Bone Density Conservation Agents
  • Zoledronic Acid