贝沙罗汀软胶囊在复发难治性皮肤T细胞淋巴瘤患者中的Ⅰ期临床研究  

Phase I study of bexarotene soft capsule in patients with relapsed or refractory cutaneous T-cell lymphoma

作　　者：董梅[1] 邢镨元[1] 石远凯[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院内科,北京100021

出　　处：《中国新药杂志》2011年第16期1539-1543,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项:抗肿瘤新药的临床评价研究技术平台建设(2008ZX09312-020)

摘　　要：目的:研究贝沙罗汀在皮肤T细胞淋巴瘤患者中的安全性及药代动力学特征,并进行初步疗效观察。方法:皮肤T细胞淋巴瘤患者接受贝沙罗汀口服300 mg.m-2,qd,连用4周。记录安全性指标,进行单剂量和多剂量药物代谢分析,观察患者病灶变化。结果:入组患者5例,每日中位服药剂量为525 mg,中位服药时间4周。常见不良反应为I～II度胃肠道反应、白细胞减少和中性粒细胞减少、头痛、发热、胆固醇升高、三酰甘油升高和甲状腺功能减退,1例患者出现III度皮疹,考虑为药物过敏,除此之外无III～IV度不良反应发生。服药d 1和连续服药d 28的Cmax分别为366.31和652.44 ng.mL-1;t1/2分别为2.56和3.18 h;AUC0～t分别为1 680.96和2 133.34 ng.mL-1.h。4例可评价疗效的患者1例病变部分缓解,2例病变稳定,1例病变进展。结论:贝沙罗汀在皮肤T细胞淋巴瘤患者中耐受性好,初步观察疗效较好,口服吸收较快,连续服药有一定蓄积作用。推荐首先在皮肤T细胞淋巴瘤患者中进行II期临床研究,剂量为300 mg.m-2,每日1次口服。Objective：Bexarotene is a retinoid X receptor（RXR）-selective retinoid that has demonstrated clinical efficacy in patients with cutaneous T-cell lymphoma（CTCL） in early-and advanced-stages.In this phase I study,we evaluated the safety and pharmacokinetics（PKs） of bexarotene in patients with relapsed or refractory CTCL.Methods：Five patients with refractory or relapsed CTCL were enrolled in this study.Bexarotene soft capsules（300mg·m-2） were orally administered once daily for 4 consecutive weeks.Safety indexes,and single-or multi-dose PKs were determined,and the cutaneous foci were observed.Results：In the 5 patients,the adverse events included G1 and G2 nausea and vomiting,headache,fever,hypertriglyceridemia and hypothyroidism.One patient experienced a G3 hypersensitivity reaction.Cmax values of bexarotene at the 1st day and 28 days after consecutive administration were 366.31 and 652.44ng·mL-1;t1/2 were 2.56 and 3.18h;AUC0-t were 1680.96 and 2133.34ng·mL-1·h,respectively.In 4 evaluable patients,1 patient achieved PR,2 patients experienced SD,and 1 patient experienced PD.Conclusion：Bexarotene is well-tolerated in patients with refractory or relapsed CTCL.Preliminary results show a good response in these patients.PK analysis suggests that increased systemic exposure may occur after multi-dose administration of bexarotene on a 300mg·m-2 orally once daily schedule.We recommend that further phase II study should be firstly done in patients with refractory or relapsed CTCL.The oral dose of 300mg·m-2 once daily is recommended for phase II study.

关 键 词：贝沙罗汀 I期临床研究 耐受性 药动学 皮肤T细胞淋巴瘤 

分 类 号：R979.1[医药卫生—药品]