New Orleans—Various chemotherapeutic agents are associated with the development of hyponatremia. Despite good overall outcomes, use of those agents may be limited by severe, symptomatic hyponatremia.
During a poster session at Kidney Week 2017, Ari B. Geller, MD, reported a case study of a patient with a history of metastatic renal cell carcinoma with sarcomatoid who presented to the emergency department (ED) with one week of progressive fatigue, decreased energy levels, unsteadiness, lightheadedness, and poor oral intake. The patient was a white male, 62 years of age. Three weeks prior to his visit to the ED, the patient was started on the new anti-VEGF agent, carbozantinib, following failure of his previous therapy.
The patient was euvolemic on physical examination in the ED. Despite known brain metastases, a complete neurologic examination was normal. Results of laboratory tests revealed sodium 112 mEq/L (compared with 131 two weeks prior), potassium 4.1 mmol/L, blood urea nitrogen 16 mmol/L, creatinine 0.6 mg/dL, serum osmolality 229 mOsm/kg, urine osmolality 645 mOsm/kg, urine sodium 125 mEq/L, thyroid-stimulating hormone 2.42 mIU/L, morning cortisol level 6.8 mcg/dL.
Based on those rest results, the patient was thought to have SIADH (syndrome of inappropriate antidiuretic hormone) secretion. He was on a long-term selective serotonin reuptake inhibitor at a stable dose. Head imaging showed metastatic brain lesions that had decreased in size.
Despite restriction of fluid, serum sodium dropped to 110 mEq/L. Hypertonic saline 3% was started, followed by torsemide and salt tablets. A co-syntropin stimulation yielded inadequate results. However, he had been normotensive and did not receive corticoid therapy during hospitalization or at discharge. His sodium level improved and was at 133 mEq/L at discharge, and at 137 2 days following.
He received treatment with dose-reduced carbozantinib as an outpatient; however, within 2 weeks his sodium level dropped to 128 mEq/mL and the therapy was dropped.
In summary, Dr. Geller said, “Carbozantinib was FDA approved in April 2016 for use in patients with advanced renal cell carcinoma who have failed prior anti-VEGF therapy. It improves progression-free survival in patients with advanced renal cell cancer with cancer of prior therapy (P<.005) when compared to everolimus, which is standard of care. In the phase 1 trial of the drug, two out of 25 participants developed hyponatremia. In the phase 2 and phase 3 trials, hyponatremia was not reported. The most commonly seen adverse effects were diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. This is the first known reported case of severe, symptomatic hyponatremia secondary to SIADH attributed to carbozantinib therapy.”
Source: Geller AB. Severe symptomatic hyponatremia in patient started on new anti-VEGF therapy. Abstract of a poster presented at the American Society of Nephrology 2017 Kidney Week, November 2, 2017, New Orleans, Louisiana.