A case of hyperammonemia occurring during treatment of metastatic renal cell carcinoma with axitinib.

Introduction: Although the incidence of hyperammonemia as an adverse event of tyrosine kinase inhibitors is quite low, several cases of tyrosine kinase inhibitor associated hyperammonemia have been reported. We report a case of hyperammonemia, that occurred during combined treatment with axitinib and pembrolizumab in a metastatic renal cell carcinoma patient without hepatic disorder or liver metastases.

Case Presentation: A 77-year-old Japanese woman was diagnosed with metastatic renal cell carcinoma and was treated with pembrolizumab and axitinib. Both agents were subsequently discontinued due to hyperammonemia with hypothyroidism. After recovery, the patient resumed single-agent therapy with axitinib. However, hyperammonemia and hypothyroidism occurred again, suggesting axitinib-inducible adverse event. After nephrectomy, a lower dose of axitinib was restarted and continued safely for residual metastases under prophylactic treatment with aminoleban, lactulose, and levothyroxine.

Conclusion: The rare occurrence of hyperammonemia should be considered during treatment with VEGFR- targeted tyrosine kinase inhibitor including axitinib, and supportive prophylactic medication may be useful.