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Medline ® Abstract for Reference 216

of 'Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials'

Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study.
Tejpar S, Piessevaux H, Claes K, Piront P, Hoenderop JG, Verslype C, Van Cutsem E
Lancet Oncol. 2007;8(5):387.
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.
Digestive Oncology Unit, Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium. sabine.tejpar@uz.kuleuven.ac.be