Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
Target Oncol. 2015 Sep;10(3):429-37. doi: 10.1007/s11523-014-0349-2. Epub 2014 Dec 13.
An attenuated dosing (AD) regimen of 37.5 mg daily in repeated 4 week on, 2 week off cycles has been proposed to ameliorate frequent dose modifications caused by the toxicity observed with the approved dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC). This study aimed to determine the effect of drug exposure on toxicity and clinical response in patients receiving this regimen. All mRCC patients receiving AD sunitinib were invited to participate. In week 4 of each cycle, toxicity and plasma levels were assessed. Clinical responses were assessed after two cycles. A total of 36 patients were recruited. Patients who manifested ≥grade 2 mucositis (126.46 vs 84.81 ng/mL, p = 0.04) and altered taste (159.91 vs 105.22 ng/mL, p = 0.05) had higher total exposure than those who had grade 1 or no toxicity. Twenty-six patients completed two treatment cycles; four (15%) had partial responses, 15 (58%) had a stable disease and 7 (27%) had progressive disease. No difference in the exposure levels was found among the patients with different clinical outcomes. The AD regimen of sunitinib in Asian mRCC patients provided sufficient drug exposure with a lower incidence of toxicity, with higher drug exposure being observed in patients who experienced toxicity.
一种每日 37.5 毫克的减毒剂量（AD）方案，每 4 周重复一次，2 周停药周期，已被提议用于改善转移性肾细胞癌（mRCC）患者因舒尼替尼批准剂量方案引起的毒性而频繁进行剂量调整的情况。本研究旨在确定接受该方案治疗的患者的药物暴露对毒性和临床反应的影响。所有接受 AD 舒尼替尼治疗的 mRCC 患者均被邀请参加。在每个周期的第 4 周，评估毒性和血浆水平。在两个周期后评估临床反应。共招募了 36 名患者。表现出≥2 级粘膜炎（126.46 与 84.81ng/mL，p=0.04）和味觉改变（159.91 与 105.22ng/mL，p=0.05）的患者总暴露量高于仅表现出 1 级毒性或无毒性的患者。26 名患者完成了两个治疗周期；4 名（15%）有部分缓解，15 名（58%）病情稳定，7 名（27%）病情进展。不同临床结局的患者之间暴露水平无差异。亚洲 mRCC 患者的 AD 舒尼替尼方案提供了足够的药物暴露，毒性发生率较低，在出现毒性的患者中观察到更高的药物暴露。
