Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study.
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.


RESULTS
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.


CONCLUSIONS
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.
Tejpar
Sabine
S
Digestive Oncology Unit, Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium. sabine.tejpar@uz.kuleuven.ac.be
Piessevaux
Hubert
H
Claes
Kathleen
K
Piront
Patricia
P
Hoenderop
Joost G J
JG
Verslype
Chris
C
Van Cutsem
Eric
E
D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology*; D005260:Female; D006801:Humans; D008274:Magnesium / Q000097:blood / Q000652:urine; D008275:Magnesium Deficiency / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D008274:Magnesium; D000068818:Cetuximab