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Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a
Sabine Tejpar1, Hubert Piessevaux, Kathleen Claes
1Digestive Oncology Unit, Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium. sabine.tejpar@uz.kuleuven.ac.be
Background:
Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this side-effect is unknown, and if all or a subset of patients are affected is also unclear. We aimed to assess the incidence, characteristics, and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies, and to study the pathophysiology of this phenomenon.
Methods:
We measured prospectively magnesium concentrations in a cohort of 98 patients with colorectal cancer treated with EGFR-targeting antibodies with or without combined chemotherapy. The primary outcome measure was the slope of the serum magnesium concentrations over time. In 35 patients, 24-h urinary magnesium excretion was measured. In a subset of patients (n=5), an intravenous magnesium load test was done. 16 patients who had chemotherapy alone acted as controls. A clinical protocol was written before initiation of the study, but because this was a non-interventional study, the protocol was not formally registered.
Findings:
95 (97%) patients had decreasing serum magnesium concentrations during EGFR-targeting treatment compared with baseline measurements. The mean serum magnesium slope during EGFR-targeting treatment (with or without combined chemotherapy) was significantly lower compared with chemotherapy alone (-0.00157 mmol/L/day, SD 0.00162 [95% CI -0.00191 to -0.00123] vs 0.00014 mmol/L/day, SD -00076 [-0.00026 to 0.00055]; (t test, p < 0.0001). 24-h urine analysis and intravenous magnesium load tests showed a defect in renal magnesium reabsorption.
Interpretation:
EGFR-inhibiting antibodies compromised the renal magnesium retention capacity, leading to hypomagnesaemia in most patients. Future studies should address the effects of exposure and target affinity. Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis.
Insights
Epidermal growth factor receptor (EGFR)-targeting antibodies cause magnesium wasting in most colorectal cancer patients by impairing kidney retention. This leads to hypomagnesaemia, highlighting EGFR signaling
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Preliminary evidence suggests magnesium wasting in patients receiving epidermal growth factor receptor (EGFR)-targeting antibodies for colorectal cancer.
- The mechanism and patient subset affected by this side effect remain unclear.
Purpose of the Study:
- To assess the incidence, characteristics, and predictive factors of magnesium wasting during EGFR-targeting antibody treatment.
- To investigate the pathophysiology of EGFR-antibody-induced magnesium wasting.
Main Methods:
- Prospective measurement of serum magnesium concentrations in 98 colorectal cancer patients treated with EGFR-targeting antibodies.
- Assessment of 24-h urinary magnesium excretion and intravenous magnesium load tests in subsets of patients.
- Comparison with a control group of 16 patients receiving chemotherapy alone.
Main Results:
- 97% of patients (95/98) exhibited decreasing serum magnesium concentrations during EGFR-targeting treatment.
- A significant difference in mean serum magnesium slope was observed between EGFR-targeting antibody treatment and chemotherapy alone (p < 0.0001).
- Urinary excretion and magnesium load tests indicated a defect in renal magnesium reabsorption.
Conclusions:
- EGFR-inhibiting antibodies compromise renal magnesium retention, leading to hypomagnesaemia in the majority of patients.
- The EGFR-signaling pathway plays a crucial role in regulating magnesium homeostasis.
- Future research should explore exposure effects and target affinity in relation to magnesium wasting.
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