NDT Plus Advance Access originally published online on April 7, 2008
NDT Plus 2008 1(3):196-197; doi:10.1093/ndtplus/sfn039
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Impact of cetuximab conventional dosing on cetuximab-induced magnesium concentration under haemodialysis in head and neck cancer
1 Department of Radiation Oncology, Centre Lacassagne, Nice
2 Department of Nephrology Hospital Pitié-Salpêtrière, Paris
3 Department of Medical Oncology Centre Lacassagne
4 Department of Head and Neck Surgery, CHU Pasteur, Nice, France
Correspondence: E-mail: jthariat{at}hotmail.com
Sir,
Cetuximab-induced hypomagnesaemia is a concern in 50% of patients with normal renal function, including 15% of chronic kidney disease (CKD) stages 3–4 [1]. Cetuximab, a 150 kDa anti-EGFR (epidermal growth factor) monoclonal antibody (MAb), has been approved for the treatment of locally advanced cancer of the head and neck (LACHN) [2] but data in patients undergoing chronic dialysis are scarce. It may be assumed that the risk for electrolyte disorders increases under dialysis with the use of cetuximab.
A 55-year-old Caucasian man on home haemodialysis presented with unresectable LASCCHN (locally advanced squamous cell cancer of the head and neck). End-stage renal disease (ESRD) resulted from polycystic kidney disease (PKD). Baseline blood abnormalities included haemoglobin (8.9 g/dl) and fibrinogen (6.9 g/l). Magnesium (0.87 mmol/l; 0.7–1) and calcium (2.33 mmol/l; 2.10–2.55) levels were normal. The dialysate contained sodium 103 mmol/l, potassium 2 mmol/l, calcium 1.5 mmol/l, bicarbonates 35 mmol/l and no magnesium. Cetuximab was given at a loading dose of 400 mg/m2 followed by seven weekly doses of 250 mg/m2. Electrolyte counts, including magnesium levels (0.84–0.99 mmol/l), remained normal from the initiation of treatment to Week 20. Complete tumour response was achieved 2 months following completion of treatment.
Cetuximab-induced hypomagnesaemia is associated with age, baseline magnesium concentration and prolongation of treatment [1]. The EGFR is normally localized to the basolateral surface of renal epithelial cells lining collecting tubules. EGFR mislocalization to the apical surface in PKD is accompanied by EGFR increased protein level and tyrosine kinase activity. Cetuximab-induced inappropriate urinary excretion may result from EGFR overexpression in Henle's ascending loop, where 70% of magnesium is passively reabsorbed, due to an MAb-specific phenomenon. The other 30% is reabsorbed by one half by the proximal and distal tubules. Inadequate EGFR stimulation results in insufficient activation of the epithelial magnesium channel protein TRPM6 and thereby magnesium loss [3,4]. There are no data on hypomagnesaemia after cetuximab in ESRD patients. In patients on renal replacement therapy, magnesium homeostasis no longer occurs through the kidney and ESRD patients are more likely to develop hypermagnesaemia due to a lack of renal excretion in cases of excessive magnesium levels. Due to the mechanism described for cetuximab-induced hypomagnesaemia, which occurs through deregulation of renal magnesium reabsorption, it is unlikely to be observed in patients with damaged kidneys, i.e. in haemodialysis patients. As a result, we believe that, in haemodialysis patients, the risk for cetuximab-induced hypomagnesaemia is very low.
An important implication for the practicing oncologist was that conventional cetuximab dosing might be used in haemodialysis patients. Since haemodialysis patients now have a better life expectancy and MAb have limited toxicity, we suggest that haemodialysis patients should not be denied optimal treatment on the sole basis of their renal replacement. Translational research is needed to elucidate the mechanisms of MAb-induced electrolyte disorders at the level of the normal and damaged kidneys.
Conflict of interest statement. None declared.
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