EGFR-Targeted Therapies for Colorectal Cancer Linked to Lower Magnesium

LEUVEN, Belgium. May 1 -- Epidermal-growth-factor receptor (EGFR) antibodies used for colorectal cancer treatment led to magnesium wasting for 95 of 98 patients, found investigators here.

With or without concurrent chemotherapy, the EGFR-targeting treatment was associated with a significantly lower serum magnesium slope (P

Serum magnesium concentrations were assessed at baseline and every two weeks. Twenty-four hour urine collections were not pre-planned but were obtained at baseline from 15 patients and on treatment in 35 patients.

Among the findings:

• A progressive decrease in serum magnesium concentrations was observed in 97% of patients.
• The rate of magnesium loss and the duration of treatment determine the onset of hypomagnesaemia during treatment with EGFR-targeted therapy.
• Increasing age was associated with more severe magnesium wasting.
• Higher baseline serum magnesium concentrations were associated with steeper slopes, suggesting that baseline differences in magnesium regulation influence on-treatment magnesium wasting.
• After discontinuation of EGFR inhibition there was rapid magnesium recovery.
• Weekly intravenous magnesium substitution did not correct serum magnesium depletion, but daily intravenous magnesium was effective in the acute setting.

In an editorial that accompanied the study, Marwan Fakih, M.D., of the Roswell Park Cancer Institute in Buffalo, N.Y., wrote that the "Tejpar study is the first to show that some degree of hypomagnesaemia occurs in almost all patients receiving EGFR-targeting monoclonal antibodies."

He said that Roswell Park has "implemented a cetuximab stop-and-go approach in patients with grade 3 and above hypomagnesemia needing more than three-times weekly infusions of intravenous magnesium replacement. Our experience confirmed the complete resolution of hypomagnesemia within two months of stopping, and the feasibility of rechallenge with cetuximab when magnesium concentrations return to normal."

He added, hypomagnesemia "recurs rarely within two months from the start of cetuximab rechallenge."

But developing effective preventive strategies against hypomagnesemia will require a better understanding of the mechanism of anti-EGFR induced magnesium wasting. He concluded that comprehensive studies of "EGFR polymorphisms in patients with and without severe hypomagnesemia after treatment with anti-EGFR monoclonal antibodies might shed further light on this toxicity."