Segarra Ignacio, Modamio Pilar, Fernández Cecilia, Mariño Eduardo L
Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avn. Joan XXIII, s/n, Barcelona, 08028, Spain.
Clin Drug Investig. 2016 Oct;36(10):791-9. doi: 10.1007/s40261-016-0428-5.
Sunitinib is a tyrosine kinase inhibitor used for the treatment of renal cell carcinoma and metastatic brain tumors. Preclinical pharmacokinetic studies have shown higher sunitinib hepatic and brain exposure in female mice and higher sunitinib kidney concentrations in male mice. We explored whether sex-divergent tissue pharmacokinetics may anticipate sex-divergent therapeutic and toxicology responses in male and female patients. The review of the available scientific literature identified case reports, case series reports, clinical trials, and other studies associating sex with sunitinib outcomes. The results suggest male patients may respond better to renal cell carcinoma treatment and female patients may have better brain tumor treatment outcomes but a higher incidence of adverse events. Although more high-quality evidence is needed, these results, as anticipated by the preclinical data, may indicate possible sunitinib sex-divergent therapeutic outcomes in patients. In addition, we propose the systematic analysis of sex-based outcomes in clinical trial reports and their inclusion and review in the ethics committees and review boards to prevent, amongst others, patient burden in upcoming clinical trials.
舒尼替尼是一种酪氨酸激酶抑制剂，用于治疗肾细胞癌和转移性脑肿瘤。临床前药代动力学研究表明，雌性小鼠体内舒尼替尼的肝脏和脑部暴露量较高，而雄性小鼠体内舒尼替尼的肾脏浓度较高。我们探讨了性别差异的组织药代动力学是否可以预测男性和女性患者在治疗和毒理学反应上的性别差异。对现有科学文献的回顾确定了病例报告、病例系列报告、临床试验以及其他将性别与舒尼替尼治疗结果相关联的研究。结果表明，男性患者可能对肾细胞癌治疗反应更好，而女性患者可能在脑肿瘤治疗方面有更好的结果，但不良事件发生率较高。尽管需要更多高质量的证据，但这些结果正如临床前数据所预期的那样，可能表明患者使用舒尼替尼时存在性别差异的治疗结果。此外，我们建议对临床试验报告中基于性别的结果进行系统分析，并将其纳入伦理委员会和审查委员会进行审议，以避免在即将开展的临床试验中给患者带来负担等问题。
