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Management of adverse events of targeted therapies in normal and special patients with metastatic renal cell carcinoma

机译:正常和特殊转移性肾细胞癌患者靶向治疗不良事件的管理

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摘要

Treatment options for metastatic renal cell carcinoma (mRCC) have evolved very rapidly, as reflected by the approval of the many drugs that have shown efficacy in phase III studies. Approved drugs include tyrosine kinase inhibitors (TKI) such as sunitinib, sorafenib and pazopanib, vascular endothelial growth factor inhibitors such as bevacizumab, and mammalian target of rapamycin (mTOR) inhibitors such as temsirolimus and everolimus. These biological agents have toxicity profiles that differ from those accompanying current chemotherapeutic agents, but their novelty leads to a lack of exhaustive clinical data regarding related adverse events (AEs), whose symptoms may overlap with those of the chronic illnesses of patients with mRCC such as hypertension, hyperglycemia, and pneumonitis. Hypertension, hypothyroidism, hand–foot syndrome, and fatigue are AEs frequently associated with TKIs; whereas immunosuppression, stomatitis, metabolic alterations, and non-infectious pneumonitis are AEs of mTOR inhibitors. Recommendations for treating these adverse events in patients with mRCC are usually the same as those for the general population. Mild to moderate toxicities may be managed with supportive and pharmacologic interventions, but higher-grade toxicities usually require external specialist consultation, dose reductions, and treatment interruption or discontinuation. Some groups of patients with mRCC, such as frail, elderly patients, and patients with renal or liver dysfunction, require special management of AEs.
机译:转移性肾细胞癌(mRCC)的治疗选择发展非常迅速,这反映了许多在III期研究中显示出疗效的药物的批准。批准的药物包括酪氨酸激酶抑制剂(TKI)(例如舒尼替尼,索拉非尼和帕唑帕尼),血管内皮生长因子抑制剂(例如贝伐单抗)和雷帕霉素(mTOR)抑制剂的哺乳动物靶标(例如西罗莫司和依维莫司)。这些生物制剂的毒性谱不同于目前的化学治疗剂,但它们的新颖性导致缺乏有关不良事件(AE)的详尽的临床数据,这些不良事件的症状可能与mRCC患者的慢性疾病如高血压,高血糖症和肺炎。高血压,甲状腺功能减退,手足综合征和疲劳是经常与TKI相关的AE。而免疫抑制,口腔炎,代谢改变和非感染性肺炎是mTOR抑制剂的AE。治疗mRCC患者的这些不良事件的建议通常与普通人群的建议相同。轻度至中度毒性可以通过支持性和药物干预进行管理,但更高级别的毒性通常需要外部专家咨询,降低剂量以及治疗中断或中止。某些mRCC患者组,例如体弱,老年患者以及肾或肝功能不全患者,需要对AE进行特殊处理。

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