Management of Metabolic Effects Associated With Anticancer Agents Targeting the PI3K-Akt-mTOR Pathway
Management of Metabolic Effects Associated With Anticancer Agents Targeting the PI3K-Akt-mTOR Pathway
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DOI：
10.1200/jco.2011.39.7356
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发表时间：
2012-08-10
影响因子：
45.3
通讯作者：
Siu, Lillian L.
中科院分区：
文献类型：
--
作者：
Busaidy, Naifa L.;Farooki, Azeez;Siu, Lillian L.
抑制磷酸肌醇3-激酶-Akt-哺乳动物雷帕霉素靶点（PAM）通路的药物目前处于肿瘤学临床开发的各个阶段，从早期评估中的一些到已经获得监管批准用于治疗晚期癌症的其他药物。PAM途径抑制剂的施用与高脂血症和高血糖症的代谢毒性相关。美国国家癌症研究所研究药物指导委员会的PAM工作组召集了一个跨学科专家小组，审查PAM通路抑制剂诱导的高脂血症和高血糖症的病理生理学，总结当前文献中此类药物诱导的这些代谢毒性的发生率，对临床试验筛选和监测标准提出建议，并对这些毒性的发生提供管理指导和治疗目标。本共识报告的总体目标是提高对这些代谢不良事件的认识，以便在临床试验中早期识别、定期监测和及时干预。高脂血症和高脂血症通常没有急性毒性，并且通常通过治疗干预可逆。只有在重度事件的情况下，或者在尝试治疗干预足够长时间后进行性代谢紊乱持续存在的情况下，才应考虑调整PAM通路抑制剂的剂量或停用PAM通路抑制剂。应寻求专业咨询，以帮助临床试验计划和这些代谢不良事件的管理。
Agents inhibiting the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (PAM) pathway are currently in various stages of clinical development in oncology, ranging from some in early-phase evaluations to others that have already received regulatory approval for treatment in advanced cancers. The administration of PAM pathway inhibitors has been associated with metabolic toxicities of hyperlipidemia and hyperglycemia. The PAM Task Force of the National Cancer Institute Investigational Drug Steering Committee convened an interdisciplinary expert panel to review the pathophysiology of hyperlipidemia and hyperglycemia induced by PAM pathway inhibitors, summarize the incidence of these metabolic toxicities induced by such agents in the current literature, advise on clinical trial screening and monitoring criteria, and provide management guidance and therapeutic goals on occurrence of these toxicities. The overarching aim of this consensus report is to raise awareness of these metabolic adverse events to enable their early recognition, regular monitoring, and timely intervention in clinical trials. Hyperglycemia and hyperlipidemia are generally not acutely toxic and most often reversible with therapeutic intervention. Dose modifications or discontinuation of PAM pathway inhibitors should only be considered in situations of severe events or if progressive metabolic derangement persists after therapeutic interventions have been attempted for a sufficient duration. Specialty consultation should be sought to aid clinical trial planning and the management of these metabolic adverse events.