Progressive decrease of serum magnesium levels occurs in virtually all patients treated with anti-EGFR antibodies. This is supposedly linked to an inhibition of renal TRPM6 activity. This Mg loss may ultimately require stopping the anti-cancer treatment. In patients with congenital TRPM6 deficiency, high dose oral Mg supplementation allows to maintain acceptable serum Mg levels but may induce significant diarrhea. We hypothesized that oral Mg gluconate substitution may prevent and/or treat Mg wasting due to anti-EGFR treatment in colorectal cancer (CRC).
We performed a prospective randomized multi-centre trial in patients treated with anti-EGFR antibodies for CRC evaluating the efficacy and tolerability of oral Mg gluconate for prevention and/or treatment of Mg wasting. Upon initiation of anti-EGFR treatment, patients were randomized to no intervention (arm A) or Mg gluconate 3 g bid (arm B). After occurrence of hypomagnesaemia grade 1, Mg gluconate 3 g bid was initiated in arm A, whereas the dosage was increased to 3g 6 times daily in arm B. The co-primary outcome variables were the slope of the serum Mg levels since baseline and the mean number of bowel movements per day. An a priori statistical analysis plan estimated the need to screen 180 patients (β = 0.90) to demonstrate an effect on serum Mg slopes.
After excluding 7 patients during screening, 89 were randomized to arm A (no intervention) and 84 to arm B (Mg supplementation). In an ITT approach, the mean serum Mg slope was significantly (p = 0.015) steeper in arm A: -0.0045 (95%CI: -0.0062 to -0.0034) vs. -0.0021 (95%CI: -0.0037 to -0.0009) mg/dl/day in arm B. Hypomagnesaemia occurred in 12 and 4 patients respectively (p = 0.05). This lead to insufficient number of patients to draw conclusions for the second part of the trial. The mean number of bowel movements was not different across arms. Oral Mg supplementation was not associated to significant adverse events.
This prospective randomized trial demonstrated that oral Mg gluconate 3 g bid. significantly decreased Mg wasting during anti-EGFR treatment in colorectal cancer, thereby delaying the occurrence of hypomagnesemia. This treatment was well tolerated.
Clinical trial identification
Legal entity responsible for the study
Belgian Group of Digestive Oncology.
Has not received any funding.
All authors have declared no conflicts of interest.