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Pazopanib-related tumor lysis syndrome in metastatic clear cell renal cell carcinoma: a case report

机译:与转移透明细胞肾细胞癌中的Pazopanib相关肿瘤裂解综合征:案例报告

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摘要

Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib. Discussion The pharmacokinetics and phamiacodynamics of pazopanib are complex and characterized by a non-linear and time-dependent bioavailability. Pazopanib is almost completely bound to serum albumin (99.9%). In this presented case, a low serum albumin (26 g/L) might have led to a higher free fraction of pazopanib, which could have resulted in more toxicity. Also, pazopanib is metabolised by the CYP3A4 isoform of the cytochrome P450 group. Low quantities of this enzyme may lead to an impaired and prolonged breakdown of the drug. Conclusion As far as we know this is the first report on pazopanib induced TLS. We advise further research in order to identify the exact mechanism behind TKI-induced TLS and the patients at risk of developing TLS.
机译:引言肿瘤裂解综合征(TLS)是由于抗肿瘤治疗的快速细胞死亡引起的危及生命的应急。在靶向治疗的时代,它越来越多地观察到肝细胞癌(HCC)和肾细胞癌(RCC)等固体恶性肿瘤中观察到。案例我们描述了一个58岁男性的案例,其中一名58岁的男人纪念斯隆kettering癌症中心(mskcc)预后差的透明细胞肾细胞癌(MRCC)在用酪氨酸激酶启动治疗后六天内开发TLS的透明细胞肾细胞癌(MRCC)抑制剂(TKI)Pazopanib。讨论Pazopanib的药代动力学和噬菌体性能是复杂的,其特征在于非线性和时间依赖性生物利用度。 Pazopanib几乎完全融合到血清白蛋白(& 99.9%)。在该呈现的情况下,低血清白蛋白(26g / L)可能导致了更高的Pazopanib的自由分数,这可能导致毒性更多。此外,Pazopanib由细胞色素P450组的CYP3A4同种型代谢。低量的这种酶可能导致药物的受损和长时间崩溃。结论据我们所知,这是Pazopanib诱发TLS的第一个报告。我们建议进一步的研究,以确定TKI诱导的TLS背后的确切机制,患者有患有TLS的风险。

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