Goldman Jonathan W, Mendenhall Melody A, Rettinger Sarah R
Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Santa Monica, California, USA
Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Santa Monica, California, USA.
Oncologist. 2016 Nov;21(11):1326-1336. doi: 10.1634/theoncologist.2015-0519. Epub 2016 Jul 29.
: Molecularly targeted cancer therapy has rapidly changed the landscape of oncologic care, often improving patients' prognosis without causing as substantial a quality-of-life decrement as cytotoxic chemotherapy does. Nevertheless, targeted agents can cause side effects that may be less familiar to medical oncologists and that require the attention and expertise of subspecialists. In this review, we focus on hyperglycemia, which can occur with use of new anticancer agents that interact with cell proliferation pathways. Key mediators of these pathways include the tyrosine kinase receptors insulin growth factor receptor 1 (IGF-1R) and epidermal growth factor receptor (EGFR), as well as intracellular signaling molecules phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). We summarize available information on hyperglycemia associated with agents that inhibit these molecules within the larger context of adverse event profiles. The highest incidence of hyperglycemia is observed with inhibition of IGF-1R or mTOR, and although the incidence is lower with PI3K, AKT, and EGFR inhibitors, hyperglycemia is still a common adverse event. Given the interrelationships between the IGF-1R and cell proliferation pathways, it is important for oncologists to understand the etiology of hyperglycemia caused by anticancer agents that target those pathways. We also discuss monitoring and management approaches for treatment-related hyperglycemia for some of these agents, with a focus on our experience during the clinical development of the EGFR inhibitor rociletinib.
Treatment-related hyperglycemia is associated with several anticancer agents. Many cancer patients may also have preexisting or undiagnosed diabetes or glucose intolerance. Screening can identify patients at risk for hyperglycemia before treatment with these agents. Proper monitoring and management of symptoms, including lifestyle changes and pharmacologic intervention, may allow patients to continue benefiting from use of anticancer agents.
分子靶向癌症治疗迅速改变了肿瘤护理的格局，通常能改善患者的预后，且不会像细胞毒性化疗那样导致生活质量大幅下降。然而，靶向药物可能会引起一些副作用，医学肿瘤学家对此可能不太熟悉，需要专科医生的关注和专业知识。在本综述中，我们重点关注高血糖症，它可能在使用与细胞增殖途径相互作用的新型抗癌药物时出现。这些途径的关键介质包括酪氨酸激酶受体胰岛素生长因子受体1（IGF-1R）和表皮生长因子受体（EGFR），以及细胞内信号分子磷脂酰肌醇3激酶（PI3K）、AKT和雷帕霉素靶蛋白（mTOR）。我们在不良事件概况的更大背景下总结了与抑制这些分子的药物相关的高血糖症的现有信息。抑制IGF-1R或mTOR时高血糖症的发生率最高，虽然PI3K、AKT和EGFR抑制剂的发生率较低，但高血糖症仍然是一种常见的不良事件。鉴于IGF-1R与细胞增殖途径之间的相互关系，肿瘤学家了解靶向这些途径的抗癌药物引起高血糖症的病因很重要。我们还讨论了其中一些药物治疗相关高血糖症的监测和管理方法，重点是我们在表皮生长因子受体抑制剂罗西替尼临床开发过程中的经验。
治疗相关的高血糖症与几种抗癌药物有关。许多癌症患者可能还存在先前存在或未被诊断的糖尿病或葡萄糖不耐受。筛查可以在使用这些药物治疗前识别出有高血糖风险的患者。对症状进行适当的监测和管理，包括生活方式改变和药物干预，可能使患者能够继续从抗癌药物的使用中获益。
