Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: Multinational phase II-III trial results
Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: Multinational phase II-III trial results
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DOI：
10.1200/jco.2001.19.9.2456
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发表时间：
2001-05-01
影响因子：
45.3
通讯作者：
Yocum, RC
中科院分区：
文献类型：
--
作者：
Duvic, M;Hymes, K;Yocum, RC
目的：皮肤T细胞淋巴瘤（CTCL）是一种T细胞恶性肿瘤，表现为皮肤病变，对维甲酸治疗有反应。一种新的RXR选择性类维生素A（rexinoid）贝沙罗汀（Targretin，LGD 1069; Ligand Pharmaceuticals Inc，San，Diego，CA）的安全性和有效性进行了评估，作为一种单一的药物口服治疗，每日一次，在一项开放标签的研究中，难治性晚期CTCL.Patients和方法：94例活检证实的CTCL在晚期（IIB-IVB）患者在26个中心入组。五十六例患者接受初始剂量为300 mg/m2/d的口服贝沙罗汀，38例患者开始剂量超过300 mg/m2/d。结果：根据研究的主要终点分类，45%（56例中的25例）的患者在300 mg/m2/d剂量下报告了临床完全和部分缓解。在超过300 mg/m2/d时，55%（21/38）的患者有反应，包括13%（5/38）的临床完成。对于300 mg/m2/d初始剂量组，缓解后复发率为36%，预计中位缓解持续时间为299天。总体体表面积受累、中位指数病变表面积、腺病、皮肤肿瘤、瘙痒和CTCL特异性生活质量也有所改善。最常见的药物相关的不良事件包括高胆固醇血症（很少与胰腺炎），高胆固醇血症，甲状腺功能减退症，和headach.Conclusion：贝沙罗汀是第一个在一类新的药物，RXR选择性类维生素A，或rexinoids，贝沙罗汀是口服给药，安全，一般耐受性良好，可逆的副作用，是有效的治疗晚期，难治性CTCL。J Clin Oncol 19：2456-2471. (C)2001年，美国临床肿瘤学会。
Purpose: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San, Diego, CA) was evaluated as a single agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL.Patients and Methods: Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m(2)/d oral bexarotene and 38 started at more than 300 mg/m(2)/d.Results: Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m(2)/d dosing. At more than 300 mg/m(2)/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m(2)/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache.Conclusion: Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids, Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL. J Clin Oncol 19:2456-2471. (C) 2001 by American Society of Clinical Oncology.