Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University, Asahikawa, Japan.
Department of Pharmacy, Sapporo Medical University Hospital, Sapporo, Japan.
Br J Clin Pharmacol. 2021 Apr;87(4):2132-2139. doi: 10.1111/bcp.14580. Epub 2020 Nov 9.
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.
目前尚不清楚治疗药物监测（TDM）是否能改善帕唑帕尼治疗的临床疗效。我们进行了一项前瞻性队列研究，以评估 TDM 在真实世界实践中对帕唑帕尼治疗的益处。在接受药代动力学指导剂量的 25 名患者中，仅有 5 名（20%，95%置信区间 6.8-40.7%）因不良事件而停止治疗。然而，5 名（41.7%，95%置信区间 15.2-72.3%）历史对照患者包括 12 名未接受该策略的患者因不良事件而导致早期停药。与对照组常规剂量相比，PK 指导剂量显著延长了治疗中断的中位时间（252 天 vs 74 天，P =.012），降低了毒性，改善了总生存（未达到 vs 313 天，P =.002）。总之，通过 TDM 进行 PK 指导剂量调整有可能改善帕唑帕尼在常规临床实践中的治疗效果，需要更大规模的随机研究。
