12
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Tratamiento hipolipemiante de la pancreatitis aguda secundaria a hipertrigliceridemia severa por everolimus en un paciente con tumor neuroendocrino Translated title: Lipid lowering treatment of severe hypertriglyceridemia with acute pancreatitis caused by everolimus in a patient with a neuroendocrine tumor

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Resumen Everolimus es un inhibidor de mTOR, empleado en oncología y como inmunosupresor en el trasplante de órgano sólido. Sus efectos adversos a nivel metabólico son muy frecuentes, especialmente los más severos. Puede ocasionar hiperglucemia, hipercolesterolemia e hipertrigliceridemia, por lo que la monitorización de los parámetros metabólicos en las sucesivas visitas es vital para detectar e iniciar tratamientos que puedan prevenir las complicaciones. Se presenta el caso de una mujer con diagnóstico de tumor neuroendocrino intestinal que desarrolló dos pancreatitis agudas secundarias a hipertrigliceridemia severa por everolimus. Tras inicio de tratamiento con fibratos y omega-3, se normalizó la cifra de triglicéridos sin presentar nuevas complicaciones metabólicas ni digestivas secundarias al fármaco. La recomendación en pacientes con cáncer en tratamiento activo con everolimus es mantener los triglicéridos por debajo de 500 o 300 mg/dL, dependiendo de si la esperanza de vida es inferior o superior a un año, respectivamente.

          Translated abstract

          Abstract Everolimus is an mTOR inhibitor, approved as a treatment for cancer and as an immunosuppressant agent in solid organ transplantation; it frequently produces toxic metabolic effects, particularly of the most severe kind. Its use can cause hyperglycemia, hypercholesterolemia and hypertriglyceridemia; thus, metabolic values should be monitored regularly to prevent these adverse events. We present the case of a woman with an intestinal neuroendocrine tumor who developed two episodes of acute pancreatitis, secondary to severe hypertriglyceridemia caused by everolimus. After treatment with fibrates and omega-3, triglyceride levels returned to baseline, without developing new metabolic or digestive complications. Targeted levels of triglyceride for cancer patients treated with everolimus, should be below 500 or 300 mg/dL, depending on whether life expectancy is less or longer than one year, respectively.

          Related collections

          Most cited references11

          • Record: found
          • Abstract: found
          • Article: not found

          Hypertriglyceridemic pancreatitis: presentation and management.

          Hypertriglyceridemia (HTG) is reported to cause 1-4% of acute pancreatitis (AP) episodes. HTG is also implicated in more than half of gestational pancreatitis cases. Disorders of lipoprotein metabolism are conventionally divided into primary (genetic) and secondary causes, including diabetes, hypothyroidism, and obesity. Serum triglyceride (TG) levels above 1,000 mg/dl are usually considered necessary to ascribe causation for AP. The mechanism for hypertriglyceridemic pancreatitis (HTGP) is postulated to involve hydrolysis of TG by pancreatic lipase and release of free fatty acids that induce free radical damage. Multiple small studies on HTGP management have evaluated the use of insulin, heparin, or both. Many series have also reported use of apheresis to reduce TG levels. Subsequent control of HTG with dietary restrictions, antihyperlipidemic agents, and even regular apheresis has been shown anecdotally in case series to prevent future episodes of AP. However, large multicenter studies are needed to optimize future management guidelines for patients with HTGP.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Metabolic complications with the use of mTOR inhibitors for cancer therapy.

            mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies. The risk of metabolic complications with these agents is not well characterized. PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. Sixteen eligible phase II clinical trials and 8 randomized controlled clinical trials were included in a systematic review and meta-analysis and the number of metabolic related AEs (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) was extracted. Incidence rates and incident rate ratios were calculated. Twenty-four trials, including 4261 patients, were included in the calculation of the incidence rate. The average incidence rate of all grade metabolic related events was 0.70 (95% CI, 0.47, 0.93). The average incidence rate of serious (grade 3 and 4) metabolic related adverse events was 0.11 (95% CI, 0.08, 0.15). The incidence rate ratio (IRR) of a metabolic adverse event with mTOR inhibitor therapy compared with control was 2.93 (95% CI, 2.33, 3.70) and of serious grade 3 and 4 metabolic adverse events was 4.58 (95% CI, 2.86, 7.34). The IRR of all grade hyperglycemia was 2.95 (95% CI, 2.14, 4.05) and of grade 3-4 hyperglycemia was 5.25 (95% CI, 3.07, 9.00). The IRR of all grade hypertriglyceridemia was 2.49 (95% CI, 1.76, 3.52) and of grade 3-4 hypertriglyceridemia was 2.01 (95% CI, 0.65, 6.27). The IRR of all grade hypercholesterolemia was 3.35 (95% CI, 2.17, 5.18) and of grade 3-4 hypercholesterolemia was 6.51 (95% CI, 1.48, 28.59). These findings suggest a statistically significant increase in the risk of hyperglycemia, hypercholesterolemia (all grades and grade 3 and 4), and all grade hypertriglyceridemia associated with mTOR therapy when compared with control. The risk of all grade and grade 3-4, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, are increase in patients treated with mTOR inhibitors compared with control. Copyright © 2013 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Review of the proliferation inhibitor everolimus.

              Everolimus (Certican) is being developed for prevention of acute and chronic rejection of solid organ transplants. A novel proliferation inhibitor, everolimus synergies with cyclosporine to prevent and reverse acute rejection in preclinical models of kidney, heart or lung transplantation. The manifestations of chronic rejection that may contribute to graft loss are also inhibited by everolimus in preclinical models. Although everolimus is metabolised by the cytochrome P450 CYP3A isoenzyme, coadministration with cyclosporine does not alter the pharmacokinetics of cyclosporine, but cyclosporine coadministration increases exposure to everolimus. Everolimus interacts with inhibitors and inducers of this system; its clearance is reduced in patients with hepatic impairment. In an immunosuppressive regimen with cyclosporine microemulsion formulation and corticosteroids, transplant recipients treated with everolimus show low rates of acute rejection and, in one heart and one renal trial, lower rates of cytomegalovirus infection. Acute rejection rates are lower than those seen with azathioprine in cardiac transplant recipients and similar to those seen with mycophenolate mofetil in renal transplant recipients. Low rates of acute rejection are maintained when everolimus is given as part of a quadruple immunosuppressive regimen with low-dose cyclosporine in renal transplant recipients, with the added benefit of better renal function compared with full-dose cyclosporine. Use of C(2) monitoring to optimise cyclosporine exposure and enhance efficacy and safety of everolimus is planned in future studies. Hypertriglyceridaemia and hypercholesterolaemia have been associated with everolimus, but these effects are not dose-limiting. There is no clear upper therapeutic limit of everolimus. However, thrombocytopenia occurs at a rate of 17% at everolimus trough serum concentrations above 7.8 ng/ml in renal transplant recipients. There are limited safety data available in patients with trough concentrations > 12 ng/ml. Studies suggest everolimus targets primary causes of chronic rejection by reducing acute rejection, allowing for cyclosporine dose reduction (which may lead to improved renal function relative to full-dose cyclosporine) and by reducing cytomegalovirus infection and inhibiting vascular remodelling.
                Bookmark

                Author and article information

                Journal
                asisna
                Anales del Sistema Sanitario de Navarra
                Anales Sis San Navarra
                Gobierno de Navarra. Departamento de Salud (Pamplona, Navarra, Spain )
                1137-6627
                April 2020
                : 43
                : 1
                : 103-106
                Affiliations
                [2] orgnameComplejo Hospitalario de Navarra orgdiv1Servicio de Oncología Médica
                [1] orgnameComplejo Hospitalario de Navarra orgdiv1Servicio de Endocrinología y Nutrición
                Article
                S1137-66272020000100013 S1137-6627(20)04300100013
                10.23938/assn.0859
                3078ee35-b708-41ef-b1ee-7c2d979ea5c6

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 27 March 2020
                : 06 January 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 15, Pages: 4
                Product

                SciELO Spain

                Categories
                Notas Clínicas

                Everolimus,Tratamiento hipolipemiante,Hipertrigliceridemia,Lipid-lowering therapy,Pancreatitis aguda,Acute pancreatitis,Hypertriglyceridemia

                Comments

                Comment on this article