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Chemotherapy agents, corticosteroids associated with hyperglycemia
There is a significant overlap of patients with coexisting cancer and diabetes.
Most cancer patients are older than 65 years, and the self-reported incidence of diabetes in this age group is about 17%.
Several studies have shown an increased risk of certain cancers in patients with diabetes. These include liver, pancreas, colorectal, endometrial, kidney, breast and bladder cancers, as well as non-Hodgkin’s lymphoma.
Lisa K. Lohr
Other evidence indicates the prevalence of diabetes is much higher in patients with pancreatic cancer (68%) compared with controls (23.5%) and patients with other cancers (range: 19.4%-20.7% for colorectal, lung, breast and prostate cancers).
Diabetes is underdiagnosed. It is estimated that 3% to 5% of the adult population has undiagnosed diabetes. In addition, there is evidence that patients with coexisting diabetes and cancer have more infections, greater chemotherapy toxicity, and higher mortality and recurrence rates compared with patients who have cancer but do not have diabetes.
Source: Lexicomp and Micromedex databases.
Some chemotherapy agents are associated with hyperglycemia. These include oral chemotherapy and targeted treatment agents, as well as those administered intravenously. Agents from many different pharmacologic classifications and different mechanisms of action can cause hyperglycemia. Table 1 and Table 2 list antineoplastic agents with a reported hyperglycemia incidence greater than 1%.
Source: Lexicomp and Micromedex databases.
Corticosteroids are the medications most frequently administered to patients with cancer that can induce hyperglycemia. Table 3 lists some of the common indications for corticosteroid use in these patients.
Patients with cancer might experience a temporary increase in glucose levels after corticosteroid administration, but it also may unmask prediabetes or undiagnosed diabetes. In addition, it is common for corticosteroid use to worsen diabetes control in those already diagnosed with diabetes. However, it is not possible to predict if a given patient might return to normal glucose levels after steroid discontinuation.
Source: Buzdar A. Cancer. 2011; doi:10.1002/cncr.26419.
Steroids can induce a situation of relative insulin resistance. This often results in postprandial hyperglycemia. Steroid-induced hyperglycemia is related to the dose of steroid, but not the type of steroid. However, it is important to recognize the differences in relative potency. For example, the usual glucocorticoid potency is expressed as prednisone 5 mg = dexamethasone 0.75 mg.
One of the major challenges in controlling hyperglycemia induced by cancer treatments is that most agents are administered cyclically instead of continuously. The hyperglycemia treatments — usually insulin — should be modified for the “off” times, as glucose levels may or may not come down during these times. In addition, if the cancer treatment is discontinued, the antidiabetic treatment should be modified, as well.
Appropriate glucose control goals should take into consideration the cancer prognosis.
For those patients with metastatic disease and a shortened life span, tight glucose control is probably not indicated and may place that patient at unnecessary risk for hypoglycemia. One proposed set of diabetic control goals for this kind of patient includes fasting glucoses <160 mg/dL, all random glucoses <200 mg/dL and HbA1c levels <8%.
It should be remembered that the HbA1c test may be falsely low in those patients who have had blood transfusions because the parameters for HbA1c assume a normal red blood cell life. When determining glucose goals, the patient’s potential for nausea, vomiting, anorexia and diarrhea should be taken into consideration, as these patients will have a higher risk for hypoglycemia and dehydration. These diabetes control goals should help prevent acute symptoms of hyperglycemia, such as polyuria, nocturia and polydipsia. In addition, they should help prevent subacute complications such as infections, weight loss and osmotic diuresis.
In summary, many chemotherapy agents and corticosteroids can cause hyperglycemia in those cancer patients diagnosed with diabetes, as well as those who have not been diagnosed.
Appropriate glucose control goals should take into consideration the cancer prognosis, the administration schedule of the offending agent and an individual’s risk for hypoglycemia.
References:
Aggarwal G. Pancreas. 2013;42:198-201.
Busaidy NL. J Clin Oncol. 2012;30:2919-2928.
Oyer DS. J Support Oncol. 2006;4:479-483.
Vigneri P. Endocr Relat Cancer. 2009;16:1103-1123.
For more information:
Lisa K. Lohr, PharmD, BCPS, BCOP, is a clinical pharmacy specialist and oncology medication therapy management provider at the University of Minnesota Physicians Cancer Care at Fairview in Minneapolis. She also is a HemOnc Today Editorial Board member. She may be reached at the University of Minnesota Physicians Cancer Care at Fairview, 424 Harvard St. SE (MMC 114), Minneapolis, MN 55455.
Disclosure: Lohr reports no relevant financial disclosures.