Todo Maki, Kondo Hideyuki, Hayashi Taiki, Masuda Tsukasa, Okabe Takashi, Kaneko Go, Oyama Masafumi, Shirotake Suguru, Nishimoto Koshiro
Department of Pharmacy Saitama Medical University International Medical Center Saitama Japan.
Department of Uro-Oncology Saitama Medical University International Medical Center Saitama Japan.
IJU Case Rep. 2019 Aug 3;2(5):272-275. doi: 10.1002/iju5.12101. eCollection 2019 Sep.
Pazopanib, a tyrosine kinase inhibitor, and nivolumab, an immune checkpoint inhibitor, are both considered to cause hepatotoxicity with different pathophysiology. We report a case in which a patient died of severe hepatotoxicity who was presumed to have been caused by the administration of nivolumab followed by pazopanib for metastatic renal cell carcinoma.
A 74-year-old male with metastatic renal cell carcinoma was treated with nivolumab as a third-line treatment. However, nivolumab was subsequently discontinued, as it caused severe thyroiditis. About 2 months after the final dose of nivolumab was administered, pazopanib was initiated as a fourth-line treatment. The patient suffered from lethal hepatic failure and died 18 days after the initiation of pazopanib treatment. An autopsy revealed that CD8-positive lymphocytes had infiltrated the thyroid gland and liver.
The patient was considered to have died of severe hepatic failure due to the aggravation of mild nivolumab-induced immune-related hepatitis by pazopanib.
酪氨酸激酶抑制剂帕唑帕尼和免疫检查点抑制剂纳武单抗都被认为会导致具有不同病理生理学的肝毒性。我们报告了一例转移性肾细胞癌患者因严重肝毒性死亡的病例，推测这是由先使用纳武单抗后使用帕唑帕尼所致。
一名74岁的转移性肾细胞癌男性患者接受纳武单抗作为三线治疗。然而，由于其引发了严重的甲状腺炎，纳武单抗随后停药。在最后一剂纳武单抗给药约2个月后，开始使用帕唑帕尼作为四线治疗。患者出现致命性肝衰竭，并在帕唑帕尼治疗开始后18天死亡。尸检显示CD8阳性淋巴细胞浸润了甲状腺和肝脏。
该患者被认为死于严重肝衰竭，原因是帕唑帕尼加重了纳武单抗引起的轻度免疫相关肝炎。
