Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice

Division of Hematology-Oncology, Department of Medicine, Penn State Milton S Hershey Medical Center, Hershey, PA 17033-0850, USA.
Journal of Oncology Pharmacy Practice 09/2011; 17(3):197-202. DOI: 10.1177/1078155210378913
Source: PubMed


Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.

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Available from: Joseph J Drabick, Jul 16, 2014
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    • "Hypoglycaemia may also be a side effect of another drug [3]. This effect can be observed in tyrosine kinase inhibitors (TKIs) [4] in patients with normoglycaemia and diabetes [5]. One of the TKIs that reduces the concentration of glucose in the blood is sunitinib [6]. "
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    ABSTRACT: Background Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated. Methods The research was carried out on a control group (n = 6) and a group of rabbits with diabetes (n = 6). The rabbits were treated with sunitinib in the oral dose of 25 mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with validated HPLC method with UV detection. Results The comparison of the sunitinib Cmax and AUC0–∞ in the diabetic group with the control group gave the ratios of 1.63 [90% confidence interval (CI) [1.59; 1.66] and 2.03 [1.97; 2.09], respectively. Statistically significant differences between the analyzed groups were revealed for Cmax (p = 0.006), AUC0–∞ (p = 0.0088), and AUCkel (p = 0.009). The maximum glycaemia drop of 14.4–69.6% and 15.4–33.5% was observed in the diabetic animals and in the control group, respectively. The glycaemia values returned to the initial values in 24 h after the administration of the drug. Conclusions The research proved the significant influence of diabetes on the pharmacokinetics of sunitinib and it confirmed the hypoglycaemic effect of the TKI in diabetic rabbits and in normoglycaemia.
    Pharmacological reports: PR 10/2014; 66(5). DOI:10.1016/j.pharep.2014.05.011 · 1.93 Impact Factor
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    • "However, some endocrine disorders have been associated with treatment with targeted agents, including hypothyroidism (sunitinib and pazopanib), hypoglycemia (sunitinib), and hyperglycemia (everolimus) [1]. Recently, tyrosine kinase inhibitors were reported to have a potential hypoglycemic effect [2]; mean declines in blood glucose were 53 mg/dL for dasatinib, 9 mg/dL for imatinib, 12 mg/dL for sorafenib, and 14 mg/dL for sunitinib. However, the exact mechanism of this hypoglycemic effect remains unclear. "
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    ABSTRACT: Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.
    06/2014; 29(2):202-5. DOI:10.3803/EnM.2014.29.2.202
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    • "Alors que le sunitinib est proposé en deuxième ligne thérapeutique dans les recommandations françaises et européennes après la chimiothérapie, il est positionné en alternative de première ligne en cas de contre-indication à la chimiothérapie . Cependant, le risque de survenue d'hypoglycémie parfois sévère a été décrit avec le sunitinib, ce qui impose une mise en garde sur sa prescription dans l'insulinome malin [128] [129] [130]. Le mécanisme de cette baisse glycémique n'est pas encore compris. "
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    ABSTRACT: Insulinoma are malignant in 4 to 14 % of cases. Their rarity and the sparse data available in the literature have limited publication of specific guidelines for their management. The following review aim to provide up-to-date recommendations on initial evaluation including pathologic grading, measures to control hypoglycemia, antitumor strategies and long term follow-up. Will be discussed in detail respective indications of surgery, diazoxide, somatostatin analogs, everolimus, sunitinib, liver directed treatments including arterial embolization, chemotherapy and radiometabolic therapy. A Medline search using terms “insulinoma”, “neuroendocrine pancreatic tumors”, “islet cell carcinoma”, “malignant insulinoma” was performed limiting the selection to English language articles and adult age cases, along with cross referencing.
    La Presse Médicale 05/2014; 43(6). DOI:10.1016/j.lpm.2013.08.007 · 1.08 Impact Factor
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