Pharmacokinetically guided dosing has the potential to improve real-world outcomes of pazopanib
Pharmacokinetically guided dosing has the potential to improve real-world outcomes of pazopanib
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DOI：
10.1111/bcp.14580
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发表时间：
2020-11-09
影响因子：
3.4
通讯作者：
Tandai, Susumu
中科院分区：
文献类型：
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作者：
Fukudo, Masahide;Tamaki, Gaku;Tandai, Susumu
目前尚不清楚帕佐帕尼的治疗药物监测(TDM)是否在常规临床实践中改善了治疗结果。我们进行了一项前瞻性队列研究，以评估TDM在实际应用中对帕佐帕尼治疗的益处。在25例药物动力学指导给药的患者中，只有5例(20%，95%可信区间6.8-40.7%)因不良事件而停止治疗。然而，5名(41.7%，95%可信区间15.2-72.3%)的历史对照患者(包括12名未接受此类策略的患者)经历了导致提前终止的不良事件。与对照组的常规剂量相比，PK引导剂量显著延长了中位停止治疗时间(252比74天，P=.012)，降低了毒性，提高了总存活率(未达到比313天，P=.002)。总之，在常规临床实践中，通过使用TDM进行PK引导的剂量调整有可能改善帕佐帕尼的治疗结果，因此有必要进行更大规模的随机研究。
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.