Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents

Abstract

Currently, targeted anti-epidermal growth factor receptor (EGFR) agents have an important role in the treatment of various cancers. These drugs, particularly anti-EGFR monoclonal antibodies, may induce electrolyte disorders, such as hypomagnesaemia and hypocalcaemia. Early symptoms of magnesium deficiency can easily go unrecognized. However, hypomagnesaemia can in rare cases lead to serious clinical manifestations, including cardiac arrhythmias or convulsions. The elective tubular expression of renal EGF/EGFR explains the mechanism of this class-related drug side effect. Inhibition of the EGFR induces a mutated-like transient receptor potential cation channel, subfamily M, member 6 (TRPM6) syndrome, characterized by urinary magnesium and calcium wasting. The risk of hypomagnesaemia is associated with treatment duration. It is a reversible toxicity; the recovery of magnesium serum levels is usually seen 4-6 weeks of stopping the anti-EGFR antibody. Using literature from peer-reviewed journals, this review reports the clinical trials findings and discusses the mechanisms and the treatment of hypomagnesaemia induced by anti-EGFR targeted agents.

Clinical relevance and utility of cetuximab-related changes in magnesium and calcium serum levels

“…CI, confidence interval; GFR, glomerular filtration rate; log, logarithmic values; mCRC, metastatic colorectal cancer; OR, odds ratio; P, logistic regression analysis P; SCCHN, squamous cell cancer of the head and neck. levels are because of changes induced by cetuximab or secondary to changes in the kidney [17]. The phenomenon of hypomagnesemic hypocalcemia is well known [18] and may therefore contribute to the hypocalcemia in cetuximab-treated patients.…”

Patient considerations in metastatic colorectal cancer – role of panitumumab

“…Further reports show a higher incidence for EGFR mAb-induced hypomagnesemia with reports as high as 90%–100% all grades with grade 3/4 hypomagnesemia reported at 6%–47% dependent on duration of therapy with >6 months of therapy showing a higher severity incidence 53,54. Patients often will be asymptomatic.…”

“…EGFR has been shown as a regulatory factor for transient receptor potential cation channel, subfamily melastatin, member 6 (TRPM6) 53,54. TRPM6 is responsible for active magnesium reabsorption in the distal tubules, and EGFR inhibition has been linked to insufficient TRPM6 function, thus leading to magnesium wasting.…”

Hazards and risks in oncology: radiation oncology

“…Cetuximab may rarely cause hypocalemia and hypomagnesemia. When misdiagnosed the latter may proceed and cause convulsions and arrhythmia [48]. …”