Everolimus Induces Rapid Plasma Glucose Normalization in Insulinoma Patients by Effects on Tumor As Well As Normal Tissues

Fiebrich, Helle-Brit; Siemerink, E.; Brouwers, Adrienne H.; Links, Thera P.; Remkes, Wouter; Hospers, Geke A.P.; Vries, Elisabeth G.E. de

doi:10.1634/theoncologist.2010-0222

Cited by 61 publications

(57 citation statements)

References 22 publications

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“…Data on everolimus in the control of hypoglycemic symptoms have been recently published (20,21,22,23). Our study confirms these data, with the largest number of patients ever reported in the literature and a significant duration of follow-up.…”

Section: Discussionsupporting

confidence: 88%

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Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Bernard

Lombard‐Bohas

Taquet

et al. 2013

European Journal of Endocrinology

100

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Background: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option. Methods: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded. Results: Twelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1-35C months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35C months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia. Conclusion: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.

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Section: Discussionsupporting

confidence: 88%

“…In two of four patients, partial responses were observed at 16 and 29 months. Four other case reports mentioned successful efficacy of mTOR inhibitors in controlling hypoglycemia (11,21,22,23), although failure to control hypoglycemic symptoms was reported in one case (24).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Bernard

Lombard‐Bohas

Taquet

et al. 2013

European Journal of Endocrinology

100

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“…Overall, 8 retrospective studies were identified (Bernard et al 2013;Capdevila et al 2015;Ferrer-Garcia et al 2013;Fiebrich et al 2011;Kulke et al 2009;Liu et al 2016;Panzuto et al 2014;Tippeswamy et al 2015), which included a total of 183 patients with pancreatic and 135 patients with extra-pancreatic NETs (see Table 2a). …”

Section: Published Retrospective Studiesmentioning

confidence: 99%

“…Most patients were treated with everolimus as a second line drug, after failure of the previous medical treatments. Taking into account this limitation, treatment with everolimus led to disease stabilization in more than half of patients (Liu et al 2016;Tippeswamy et al 2015), and disappearance of hypoglycaemic symptoms in malignant insulinomas (Fiebrich et al 2011).…”

Section: Published Retrospective Studiesmentioning

confidence: 99%

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

Gallo

Malandrino

Fanciulli

et al. 2017

J Cancer Res Clin Oncol

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Results We identified eight retrospective published studies, two prospective published studies, and five registered clinical trials. Moreover, we analyzed the content of four widespread international guidelines. Conclusions Our critical review confirms the lack of highquality data to recommend everolimus as the first line therapy for pNETs. The ongoing clinical trials reported in this review will hopefully help clinicians, in the near future, to better evaluate the role of everolimus as the first line therapy for pNETs. However, at the moment, there is already enough evidence to recommend everolimus as the first line therapy for patients with symptomatic malignant unresectable insulin-secreting pNETs, to control the endocrine syndrome regardless of tumour growth.

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“…Pancreatic surgery reduces the amount of functional parenchyma, streptozotocin is cytotoxic to pancreatic b-cells, octreotide and everolimus reduce insulin secretion, and everolimus also increases insulin resistance (5,6). A potential consequence of these therapies is the onset of prediabetes or diabetes mellitus, which is commonly associated with increased long-term, all-cause mortality in oncologic patients (7).…”

mentioning

confidence: 99%

Diabetes Mellitus and Its Effects on All-Cause Mortality After Radiopeptide Therapy for Neuroendocrine Tumors

Radojewski

Spanjol

et al. 2016

J Nucl Med

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We aimed to assess the risk of developing diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors (NETs). Methods: NET patients received somatostatin radiopeptide therapy with 90 Y-DOTATOC or 177 Lu-DOTATOC. The incidence of diabetes mellitus and its mortality were assessed using univariate and multivariate regression. Results: Overall, 1,535 NET patients were enrolled and received 3,807 treatment cycles. After treatment, 72 patients developed diabetes mellitus, including 47 cases after 90 Y-DOTATOC and 25 cases after combined treatment. The diabetes mellitus risk was higher before than after DOTATOC (estimate, 0.0032; P , 0.001), and overall survival was similar in patients with and without diabetes mellitus (hazard ratio, 1.13; 95% confidence interval, 0.91-1.39; n 5 1,535; P 5 0.27). Conclusion: Radiopeptide therapy does not appear to increase the risk of developing diabetes mellitus in NET patients, whereas diabetes mellitus does not appear to increase the mortality of NET patients undergoing receptor-targeted radiopeptide therapy.

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Everolimus Induces Rapid Plasma Glucose Normalization in Insulinoma Patients by Effects on Tumor As Well As Normal Tissues

Cited by 61 publications

References 22 publications

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

Diabetes Mellitus and Its Effects on All-Cause Mortality After Radiopeptide Therapy for Neuroendocrine Tumors

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