[A Case of Nephrotic Syndrome Developing Early After Initiation of Fruquintinib Therapy]

Fruquintinib (FRU) is a vascular endothelial growth factor receptor (VEGFR)-1, 2, 3 tyrosine kinase inhibitor (TKI) approved for metastatic colorectal cancer. While hypertension, fatigue, and hand-foot syndrome are common adverse events, severe proteinuria and nephrotic syndrome are rare and has not been reported in clinical trials. A woman in her 60s with recurrent rectal cancer began fruquintinib at 5 mg/d as a 4th-line treatment. She had a history of hypertension and was taking amlodipine. On day 8 of the first cycle, she developed hypertension (grade 2) . On day 22, proteinuria (grade 3) was detected and hypertension had worsened (grade 3) . Since these changes occurred during the off-treatment period, observation was selected. However, on day 23, the patient presented with fatigue, generalized edema, and dyspnea. Laboratory tests revealed a urine protein/creatinine ratio of 10.3 g/gCr and elevated serum creatinine (grade 1), leading to hospitalization. Post-admission, hypermagnesemia (grade 3) was also noted. loxoprofen and magnesium oxide were discontinued and furosemide was initiated. By day 6 of hospitalization, 24-h urine protein quantification had decreased to 2.1 g/d. By day 9, edema and hypertension had both improved, and the patient was discharged. The Naranjo score were 7 for fruquintinib, 6 for loxoprofen and bevacizumab, and 5 for trifluridine/tipiracil hydrochloride, suggesting probable adverse drug reaction. VEGFR-TKIs are presumed to impair glomerular structure and function, leading to proteinuria. Although renal biopsy was not performed, thrombocytopenia and elevated lactate dehydrogenase suggested thrombotic microangiopathy. Earlier monitoring could have enabled faster detection and prevention of severe symptoms.