Pharmacokinetically guided dosing has the potential to improve real-world outcomes of pazopanib

Br J Clin Pharmacol. 2021 Apr;87(4):2132-2139. doi: 10.1111/bcp.14580. Epub 2020 Nov 9.

Abstract

It remains unclear whether therapeutic drug monitoring (TDM) of pazopanib improves treatment outcomes in routine clinical practice. We did a prospective cohort study to evaluate the benefits of TDM for pazopanib therapy in real-world practice. Among 25 patients with pharmacokinetically guided dosing, only 5 (20%, 95% confidence interval 6.8-40.7%) discontinued treatment because of adverse events. However, 5 (41.7%, 95% confidence interval 15.2-72.3%) of historical controls including 12 patients not receiving such a strategy experienced adverse events leading to early termination. PK-guided dosing significantly increased median time-to-treatment discontinuation (252 vs 74 days, P = .012) with reduced toxicity and improved overall survival (not reached vs 313 days, P = .002) relative to conventional dosing in the control group. In conclusion, PK-guided dose adaptation through the use of TDM has the potential to improve treatment outcomes of pazopanib in routine clinical practice, warranting larger, randomized studies.

Keywords: individualized dosing; pazopanib, pharmacokinetics; therapeutic drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Monitoring
  • Humans
  • Indazoles
  • Prospective Studies
  • Pyrimidines* / adverse effects
  • Sulfonamides* / adverse effects

Substances

  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Associated data

  • UMIN-CTR/UMIN000036158