Abstract: TH-PO1097

Severe, Symptomatic Hyponatremia in Patient Started on New Anti-VEGF Therapy

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

  • Jethwani, Priyanka, University of Connecticut Health Center, Hartford, Connecticut, United States
  • Geller, Ari B., None, West Hartford, Connecticut, United States
Background

Hyponatremia is described as a side-effect of various chemotherapeutic agents. However severe, symptomatic hyponatremia can often limit use of those agents despite good overall outcomes.

Methods

This is the case of a 62-year-old Caucasian male with history of metastatic renal cell carcinoma with sarcomatoid features who presented to ED with one week of progressive fatigue, decreased energy levels, unsteadiness, lightheadedness and poor oral intake. Three weeks prior, he was started on Carbozantinib (new anti-VEGF agent) after failure of prior therapy. Fluid intake was at baseline and he was euvolemic on physical examination. Complete neurologic exam was normal despite known brain metastases.

Labs revealed sodium 112 (131 two weeks ago), K 4.1, BUN 16, Cr 0.6, serum osm 229, urine osm 645, urine Na 125, TSH 2.42, AM cortisol 6.8, based on which he was thought to have SIADH. He was on long-term SSRI at a stable dose. Head imaging showed known metastatic brain lesions that had decreased in size.

Despite fluid restriction, sodium dropped to 110. 3% hypertonic saline infusion was started, followed by torsemide and salt tablets. He underwent a co-syntropin stimulation test with inadequate response. However, he had been normotensive and did not receive corticoid therapy during hospitalization or at discharge. Despite this, sodium levels improved. Sodium was 133 at discharge and 137 two days later.

He was challenged with dose-reduced Carbozantinib as outpatient, however, sodium dropped to 128 again within two weeks. Consequently, therapy was discontinued.

Conclusion

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 failure of prior therapy (p<0.005) when compared to Everolimus, which is standard of care. In the phase I trial of the drug, 2 out of 25 participants developed hyponatremia. In the phase II and phase III 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.