Background
Panitumumab is an epidermal growth factor receptor (EGFR) inhibiting monoclonal antibody approved for the treatment of RAS wild-type metastatic colorectal cancer (mCRC), which has an incidence of hypomagnesemia of approximately 35%. Grade 3 or 4 hypomagnesemia occurs in roughly 7% of patients, which can lead to serious complications such as seizures and arrhythmias. In one study, hypomagnesemia led to discontinuation of targeted therapy in 3% of patients. Currently, there is no standardized prophylactic strategy or treatment protocol for panitumumab-induced hypomagnesemia. In cases of refractory hypomagnesemia, it is recommended to discontinue panitumumab, even if the patient is deriving clinical benefit.
Case Report
This 59-year-old male was diagnosed with RAS wild-type mCRC and had already progressed through multiple lines of treatment. Panitumumab was initiated with good response; however, the drug was discontinued due to grade 4 hypomagnesemia, despite intravenous and oral supplementation. As the patient progressed through further lines of treatment, the decision was made to retry panitumumab. Grade 2-3 hypomagnesemia persisted throughout treatment, requiring frequent magnesium infusions. Innovative and alternative treatment options were investigated in an effort to improve his quality of life. In addition to oral and intravenous magnesium replacement, an ambulatory elastomeric pump, traditionally used for fluorouracil administration, was repurposed to deliver between 6 and 24 grams of magnesium sulfate over 24 to 72 hours. The pump was generally well tolerated with the exception of mild skin irritation around the port site, which prevented a transition to longer infusion times. The ambulatory elastomeric pump decreased the frequency of healthcare visits and improved the hypomagnesemia sufficiently to continue treatment with panitumumab, although levels did not fully normalize. A two-week trial of amiloride was also attempted to decrease renal magnesium wasting. Amiloride normalized magnesium levels but had to be discontinued due to asymptomatic hyperkalemia. This case report suggests that amiloride and magnesium replacement via ambulatory elastomeric pumps may be safe and effective treatment options for panitumumab-induced refractory hypomagnesemia in mCRC, potentially improving quality of life and allowing beneficial anti-cancer treatments to continue. Future studies should further evaluate optimization of amiloride and intravenous magnesium replacement via ambulatory elastomeric pump.