Management of Epidermal Growth Factor Receptor Inhibitor-Induced Hypomagnesemia: A Systematic Review

Abstract

Background: Despite occurring in 30% of patients, there are no evidence-based guidelines on the management of epidermal growth factor receptor inhibitor (EGFRI)-induced hypomagnesemia. Based on expert opinion, severe hypomagnesemia should be treated by intravenous magnesium replacement. A systematic review of published data of intervention on EGFRI-induced hypomagnesemia was performed.

Methods: Articles from 1960 to March 2015 were identified from Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed using a peer-reviewed systematic search strategy. Eligible studies included randomized controlled trials or observational studies that evaluated management of hypomagnesemia in adult patients treated with EGFRIs. Risk factors for severe hypomagnesemia were also assessed. The quality of included studies was rated using Jadad scores.

Results: A total of 1327 references were identified, and 6 studies, involving 486 patients, met inclusion criteria for analysis. There were no randomized controlled trials, and all included studies were of poor quality. From the studies included in this review, severity of EGFRI-induced hypomagnesemia was associated with length of EGFRI treatment, concomitant platinum chemotherapy, increasing age, and baseline magnesium concentration. In most patients with grade 3 or 4 hypomagnesemia, high-dose intravenous magnesium replacement did not achieve sustainable magnesium repletion beyond 72 hours. Oral magnesium supplementation was not effective or tolerable. Severe hypomagnesemia has been associated with tachycardia and mental alteration. After discontinuation of EGFRI therapy, hypomagnesemia generally resolves within weeks to months.

Conclusions: There is an absence of high-quality evidence for the management of EGFRI-induced hypomagnesemia. As hypomagnesemia is often refractory to frequent intravenous or oral replacement, there is a need for prospective trials of new interventions for this common toxicity.

Keywords: EGFR; Monoclonal antibody; Toxicity.