University of California, Davis - Hematology/Oncology, Sacramento, CA, USA.
Ther Adv Med Oncol. 2011 Mar;3(2):95-100. doi: 10.1177/1758834010396117.
Sorafenib is an oral multitargeted tyrosine and serine/threonine kinase inhibitor approved for the treatment of advanced renal cell and hepatocellular carcinoma. An understanding of its dose-toxicity relationship has paved the way for trials seeking to enhance its clinical activity through the exploration of alternative dosing strategies. In this article, we review the dose-toxicity relationship of sorafenib observed during its phase I and early phase II testing, explore its toxicity profile at the recommended dose and schedule, discuss the evidence for dose escalation to higher levels, and examine the preliminary evidence for clinical activity of this strategy. Owing to a temporal relationship between toxicity and dose, it may be possible in select patients to escalate sorafenib to doses beyond those currently employed. However, because of the potential for increased toxicity, sorafenib dose escalation should currently be performed only in the context of a clinical trial.
索拉非尼是一种口服多靶点酪氨酸和丝氨酸/苏氨酸激酶抑制剂，已被批准用于治疗晚期肾细胞癌和肝细胞癌。对其剂量毒性关系的了解为通过探索替代给药策略来提高其临床活性的试验铺平了道路。在本文中，我们回顾了索拉非尼在 I 期和早期 II 期试验中观察到的剂量毒性关系，探讨了其在推荐剂量和方案下的毒性特征，讨论了升高至更高水平的证据，并研究了这种策略的初步临床活性证据。由于毒性与剂量之间存在时间关系，因此在某些患者中，索拉非尼可能可以升高至目前使用的剂量以上。但是，由于潜在的毒性增加，索拉非尼剂量升高目前仅应在临床试验的背景下进行。
