97% of patients with cancer treated with monoclonal antibodies—cetuximab, matuzumab, or panitumumab—that target the epidermal growth factor receptor (EGFR) have some degree of magnesium loss (hypomagnesaemia), according to a study published today in the May issue of THE LANCET ONCOLOGY. "Our study is important because it shows that magnesium wasting will occur in all patients…[Previously,] hypomagnesaemia was thought to be restricted to an undefined subset of patients", says lead author Prof Sabine Tejpar. "Predicting the risk of hypomagnesaemia will also be important in those patients receiving combination treatments with nephrotoxic and potential magnesium-wasting agents, such as cisplatin."
Previous retrospective studies had shown severe magnesium loss (grades 3 and 4 hypomagnesaemia) in only a small proportion of patients given anti-EGFR drugs and whether all or a subset of patients are affected was unknown. Hypomagnesaemia is a serious side-effect of treatment as it can cause dizziness, weakness, cardiac abnormalities, or even generalised convulsions. Furthermore, agents against EGFR are being used increasingly to treat solid tumours, in particular cancers of the colorectum. However, the extent of this side-effect in patients given these antibodies has not previously been fully assessed.
Prof Sabine Tejpar and colleagues therefore studied prospectively the degree of hypomagnesaemia in 98 patients with metastatic colorectal cancer treated with these antibodies. 95 (97%) of patients had decreased serum magnesium concentrations during treatment with the EGFR-targeted antibodies compared with baseline measures (mean serum magnesium slope –0•00157 mmol/L/day [95% CI –0•00191 to –0•00123]) and this change was significantly lower than that seen in the control group not receiving antibody treatment—ie, given chemotherapy alone (0•00014 mmol/L/day [–0•00026 to 0•00055]).
In an accompanying comment, Dr Marwan Fakih (Roswell Park Cancer Institute, NY, USA) discusses the implications of the study data for clinical practice, commenting that patient characteristics, in terms of age, baseline magnesium concentrations, and duration of treatment, could help in the early identification of those at high risk. He suggests there are still a number of unanswered questions, such as whether the magnesium concentration slope could be used to predict the time at which clinically significant hypomagnesaemia will occur, and he indicates that validation of The Lancet Oncology data in a larger prospective study could help in the development of a model that accurately predicts those who are most at risk of severe hypomagnesaemia and candidates for monitoring and early intervention. In addition, Fakih proposes that intermittent treatment schedules could be appropriate for those at high risk.
The authors agree with Dr Fakih that identification of these high-risk patients is important and conclude that their study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homeostasis: "Our study might pave the way for future therapeutic intervention to treat hypomagnesaemia and modulate or prevent its occurrence".
Journal
The Lancet Oncology