title: Cetuximab therapy and symptomatic hypomagnesemia.
abstract: We report that patients treated with cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), occasionally develop a magnesium wasting syndrome with inappropriate urinary excretion. We first observed this phenomenon in a 34-year-old male patient with metastatic colorectal cancer who developed profound fatigue and symptomatic hypocalcemia and hypomagnesemia while on cetuximab plus irinotecan therapy. Other medications with the potential to cause magnesium wasting had not been administered. Intravenous magnesium supplementation was required for the duration of cetuximab therapy, but electrolyte abnormalities resolved after discontinuation of treatment. This case prompted review of serum chemistry reports for a consecutive case series of 154 colorectal cancer patients treated with cetuximab. Thirty-four patients (22%) had at least one serum magnesium measurement during cetuximab treatment, and six had grade 3 (< 0.9 mg/dL) and two had grade 4 (< 0.7 mg/dL) hypomagnesemia. Because EGFR is strongly expressed in the kidney, particularly in the ascending limb of the loop of Henle where 70% of filtered magnesium is reabsorbed, EGFR blockade may interfere with magnesium transport. Because symptoms may be rapidly ameliorated with supplementation, we suggest that, when fatigue or hypocalcemia is encountered during cetuximab therapy, serum magnesium level be measured and repleted as necessary.
authors.affiliation: Division of Gastrointestinal Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 221, New York, NY 10011, USA. schragd@mskcc.org
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Chung
authors.forename: Carlos
authors.initials: C
authors.lastname: Flombaum
authors.forename: Leonard
authors.initials: L
authors.lastname: Saltz
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005221:Fatigue / Q000209:etiology; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced* / Q000150:complications; D015994:Incidence; D000077146:Irinotecan; D008274:Magnesium / Q000097:blood*; D008275:Magnesium Deficiency / Q000139:chemically induced* / Q000150:complications; D008297:Male; D012720:Severity of Illness Index
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077146:Irinotecan; D066246:ErbB Receptors; D008274:Magnesium; D000068818:Cetuximab; D002166:Camptothecin