Monday, January 31, 2011

CONSULT ROUNDS: Cetuximab therapy and wasting syndromes?

The other day we discussed a case of cetuximab induced hypomagnesemia.
Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR; also know as c-erb1 or HER1). The EGFR is overexpressed in many epithelial cell cancers, including colorectal, breast, lung, and head and neck cancers.
This agent has been associated with mg and ca wasting syndromes.  The relationship between EGFR blockade and magnesium transport may help elucidate important cellular pathways. The protein TRPM6( for Mg transport), a member of the transient receptor potential family of cation channels, has been shown to mediate active transport. Patients with a germline mutation in the TRPM6 gene have severe congenital hypomagnesemia. TRPM6 is localized along the apical membrane of the loop of Henle and the distal convoluted tubule, as well as the brush border of the small intestine. EGFR is also highly expressed in these regions as well. Since this drug blocks EGFR, mg wasting also occurs. Urinary Mg levels usually are high in these patients if they have serum mg that is low suggesting urinary losses. Usually this effect is reversible when chemo is discontinued.
The only caviet is that this medication is usually given with irenotecan, which causes severe diarrhea as well making the diagnosis bit more difficult if the losses are GI or urinary in origin. In the setting of hypomagnesemia, PTH release and the ability of PTH to mobilize calcium from the bone are impaired leading to hypocalcemia as well.  For this reason, correction of serum magnesium is usually sufficient to normalize serum calcium levels.


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