4.5 Article

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

Journal

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 87, Issue 4, Pages 2132-2139

Publisher

WILEY
DOI: 10.1111/bcp.14580

Keywords

individualized dosing; pazopanib; pharmacokinetics; therapeutic drug monitoring

Funding

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [16 K08902]
  2. Foundation for Promotion of Cancer Research

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The results of the study suggest that using pharmacokinetic-guided dosing with TDM for pazopanib therapy can significantly improve treatment outcomes, reduce toxicity, and improve overall survival for patients. Larger, randomized studies are warranted to further confirm these findings.
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.

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