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重新审视 ALK 阳性非小细胞肺癌中阿来替尼的较低起始剂量。

Revisiting a lower starting dose of alectinib in ALK-Positive non-small cell lung cancer.

机构信息

Department of Pharmacology and Toxicology, University of the Philippines Manila College of Medicine, Taft Avenue, Manila, 1000 Philippines; Division of Medical Oncology, Department of Medicine, Philippine General Hospital and University of the Philippines Manila, Taft Avenue, Manila, 1000 Philippines.

Division of Hematology, Department of Medicine, Philippine General Hospital and University of the Philippines Manila, Taft Avenue, Manila, 1000 Philippines.

出版信息

Cancer Treat Res Commun. 2021;27:100319. doi: 10.1016/j.ctarc.2021.100319. Epub 2021 Jan 23.

Abstract

We present here a case of ALK-positive lung adenocarcinoma that has been started on Alectinib. Treatment has been initiated at the recommended initial dose, but it subsequently required a dose adjustment following adverse drug events. Alectinib is a second-generation, CNS-active, tyrosine kinase inhibitor used in the treatment of ALK-positive non-small cell lung cancer. Its efficacy as a first-line treatment and as a second-line agent after Crizotinib has been proven across several trials both in terms of overall response rate and progression-free survival. The use of Alectinib is associated with side effects that occasionally lead to treatment discontinuation, interruption, or dose adjustment. Several studies have used two starting doses - 300 mg and 600 mg twice daily - across different populations and have consistently shown efficacy of Alectinib for both treatment doses. Results of these studies have also revealed that body weight, rather than race, affect the pharmacokinetics of Alectinib. Randomized trials have shown that the 600 mg dose is associated with more grade ≥3 adverse events and more changes in treatment in contrast to the 300 mg dose. A lower dose of Alectinib may limit treatment disruptions and dose reductions particularly for specific patient populations-particularly those with a lower body weight.

摘要

我们在此介绍一例开始接受阿来替尼治疗的 ALK 阳性肺腺癌病例。该药物以推荐起始剂量开始治疗,但随后因药物不良反应需要调整剂量。阿来替尼是一种第二代、中枢神经系统活性的酪氨酸激酶抑制剂,用于治疗 ALK 阳性非小细胞肺癌。多项临床试验均证明了阿来替尼作为一线治疗和克唑替尼后二线治疗药物的疗效,在总缓解率和无进展生存期方面均有获益。阿来替尼的使用与不良反应相关,这些不良反应偶尔会导致治疗中断、中断或剂量调整。几项研究在不同人群中使用了两种起始剂量(300mg 和 600mg,每日两次),结果一致表明两种治疗剂量的阿来替尼均有效。这些研究的结果还表明,体重而不是种族会影响阿来替尼的药代动力学。随机试验表明,与 300mg 剂量相比,600mg 剂量与更多的≥3 级不良事件和更多的治疗改变相关。阿来替尼的较低剂量可能会限制治疗中断和剂量减少,特别是对于特定的患者群体——尤其是体重较低的患者。

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