Pharmacokinetics of Erlotinib and Its Active Metabolite OSI-420 in Patients with Non-small Cell Lung Cancer and Chronic Renal Failure Who Are Undergoing Hemodialysis
Pharmacokinetics of Erlotinib and Its Active Metabolite OSI-420 in Patients with Non-small Cell Lung Cancer and Chronic Renal Failure Who Are Undergoing Hemodialysis
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DOI：
10.1097/jto.0b013e3181d32287
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发表时间：
2010-05-01
影响因子：
20.4
通讯作者：
Mishima, Michiaki
中科院分区：
文献类型：
--
作者：
Togashi, Yosuke;Masago, Katsuhiro;Mishima, Michiaki
erlotinib是一种口服活性和选择性表皮生长因子受体酪氨酸激酶抑制剂，主要在肝脏代谢，但其对慢性肾功能衰竭（CRF）血液透析（HD）患者的有效性和安全性尚未报道。因此，我们研究了厄洛替尼及其活性代谢物OSI-420在这些非小细胞肺癌（NSCLC）患者中的药代动力学（PK）。方法：对3例接受HD治疗的NSCLC合并CRF患者（HD组）和5例器官功能正常的NSCLC患者（对照组）每日给予厄洛替尼150 mg，分析厄洛替尼与osi420的PK。在开始给药厄洛替尼后，HD组在第1天（停用HD）、第8天（停用HD）和第9天（停用HD）进行PK分析，对照组在第1天和第8天进行PK分析。结果：HD组第8天与第9天的PK数据差异不大。HD组第1天和第8天的PK数据也与对照组相似。所有病例均无严重不良事件发生，其中1例HD患者获得部分缓解。结论：厄洛替尼几乎不受肾功能和HD的影响，证实了厄洛替尼治疗NSCLC和CRF合并HD患者的有效性和安全性。厄洛替尼可以成为这类患者的一种治疗选择。
Introduction: Although erlotinib, an orally active and selective tyrosine kinase inhibitor of epidermal growth factor receptor, is mainly metabolized in the liver, its effectiveness and safety for patients with chronic renal failure (CRF) undergoing hemodialysis (HD) has not been reported. Thus, we investigated the pharmacokinetics (PK) of erlotinib and its active metabolite OSI-420 in such patients with nonsmall cell lung cancer (NSCLC).Method: We administered 150 mg erlotinib daily to three patients with NSCLC and CRF undergoing HD (HD group) and five patients with NSCLC and normal organ function (control group) and analyzed the PK of erlotinib and OSI-420. In the HD group, PK analyses were performed on day 1 (off HD), day 8 (off HD), and day 9 (on HD) after starting administration of erlotinib, and in the control group, they were performed on day 1 and day 8.Results: In the HD group, there were little differences in the PK data between day 8 and day 9. The PK data on day 1 and day 8 of the HD group were also similar to those of the control group. There were no serious adverse events in any cases, and one of the HD patients achieved partial response.Conclusion: Erlotinib was hardly affected by renal function and HD, which confirms the effectiveness and safety of erlotinib treatment in patients with NSCLC and CRF undergoing HD. Erlotinib can become one treatment option for such patients.