毒理性
血清氨基转移酶水平升高几乎发生在所有接受 trabectedin 治疗的患者中，超过正常上限 5 倍的升高发生在 20% 到 50% 的患者中。治疗前使用地塞米松似乎可以减少酶升高的程度和频率。升高通常发生在静脉输注后的 2 到 5 天内，在 5 到 9 天之间达到最高水平，并通常在 3 到 4 周内降至基线值。血清碱性磷酸酶和胆红素的小幅升高也很常见。然而，由于 trabectedin 引起的临床上明显的肝损伤并伴有黄疸是罕见的。另一方面，患有基础 liver 疾病的患者似乎有增加败血症和多器官衰竭的风险，建议在治疗前后监测肝功能测试。肝损伤通常模仿基础肝硬化的急性失代偿，血清酶轻度升高，黄疸和肝合成功能障碍加重。免疫过敏和自身免疫特征不常见。死亡通常是由于败血症和多器官衰竭。
Elevations in serum aminotransferase levels arise in almost all patients treated with trabectedin and elevations above 5 times the upper limit of normal occur 20% to 50% of patients. Pretreatment with dexamethasone appears to decrease the degree and frequency of enzyme elevations. The elevations arise within 2 to 5 days of the intravenous infusion, rise to maximal levels between 5 and 9 days and generally fall to baseline values within 3 to 4 weeks. Minor elevations in serum alkaline phosphatase and bilirubin are also common. However, clinically apparent liver injury with jaundice from trabectedin is rare. On the other hand, patients with underlying liver disease appear to be at increased risk for septicemia and multiorgan failure, and monitoring of liver tests before and during therapy is recommended. The liver injury typically mimics acute decompensation of an underlying cirrhosis with modest elevations in serum enzymes and worsening jaundice and hepatic synthetic dysfunction. Immunoallergic and autoimmune features are uncommon. Fatalities are generally due to sepsis and multiorgan failure.
来源:LiverTox
