Everolimus Induces Rapid Plasma Glucose Normalization in Insulinoma Patients by Effects on Tumor As Well As Normal Tissues
Everolimus Induces Rapid Plasma Glucose Normalization in Insulinoma Patients by Effects on Tumor As Well As Normal Tissues
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DOI：
10.1634/theoncologist.2010-0222
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发表时间：
2011-01-01
期刊：
影响因子：
5.8
通讯作者：
de Vries, Elisabeth G. E.
中科院分区：
文献类型：
--
作者：
Fiebrich, Helle-Brit;Siemerink, Ester J. M.;de Vries, Elisabeth G. E.
背景给予四名胰岛素瘤患者的雷帕霉素抑制剂依维莫司的哺乳动物靶点快速控制了低血糖（Kulke等人，N Engl JMed 2009; 360：195-197）。我们希望确定依维莫司控制低血糖的动力学作用并了解其潜在机制。连续3例有转移症状的胰岛素瘤患者开始接受100 μ g奥曲肽皮下注射，每日3次。由于持续性低血糖，开始每日10 mg口服依维莫司治疗。连续测量血糖水平和血清胰岛素水平。治疗前、治疗后2个月和5个月分别行CT扫描。[18F]在治疗前和治疗后2周、5周和5个月进行氟-2-脱氧-D-葡萄糖正电子发射断层扫描（F-18-FDG-PET）以观察葡萄糖代谢。F-18-FDG摄取定量为最大标准化摄取值。所有患者均在14天内通过依维莫司控制了低血糖。胰岛素水平在治疗开始前升高2.5- 6.3倍，治疗4周后下降14%-64%。CT扫描显示所有患者在2个月时病情稳定，1例患者在5个月后病情进展。治疗前，无论是肿瘤病灶还是肌肉和心肌都显示出高的F-18-FDG摄取。依维莫司治疗2周后肿瘤和肌肉F-18-FDG摄取分别降低26% ± 14%和19% ± 41%，5个月后分别降低31% ± 13%和27% ± 41%。依维莫司在14天内使转移性胰岛素瘤的血糖水平正常化，与肿瘤和肌肉中较低的葡萄糖摄取和胰岛素水平下降一致。这种对肿瘤和正常组织的作用解释了低血糖的快速控制。肿瘤学家2011;16：783-787
Background. Mammalian target of rapamycin inhibitor everolimus administered to four insulinoma patients rapidly controlled hypoglycemia (Kulke et al., N Engl JMed 2009; 360: 195-197). We wanted to identify the kinetics of everolimus effects on controlling hypoglycemia and understand underlying mechanisms.Methods. Three consecutive patients with a metastasized symptomatic insulinoma were started on 100 mu g of octreotide subcutaneously three times daily. Because of persisting hypoglycemias, treatment with daily 10 mg of oral everolimus was initiated. Serial plasma glucose levels and serum insulin levels were measured. Computer tomography (CT) scans were performed beforeandafter 2and 5 months of treatment. [18F] fluoro-2-deoxy-d-glucose positron emissiontomography (F-18-FDG-PET) scans, to visualize glucose metabolism, were made before and after 2 weeks, 5 weeks, and 5 months of treatment. The F-18-FDG uptake quantified as the maximum standardized uptake value.Results. All patients achieved control of hypoglycemia on everolimus within 14 days. Insulin levels were 2.5- to 6.3-fold elevated before start of treatment and declined 14%-64% after 4 weeks of treatment. CT scans showed stable disease at 2 months in all patients, with progressive disease after 5 months in one. Before treatment, both the tumor lesions and the muscles and myocardium showed high F-18-FDG uptake. Everolimus reduced tumor and muscle F-18-FDG uptake after 2 weeks by 26% +/- 14% and 19% +/- 41%, and after 5 months by 31% +/- 13% and 27% +/- 41%.Conclusions. Everolimus normalizes plasma glucose levels in metastatic insulinoma within 14 days, coinciding with a lower glucose uptake in tumor and muscles and declining (pro)insulin levels. This effect on tumor as well as normal tissues explains the rapid controlling of hypoglycemia. The Oncologist 2011;16:783-787