Querfeld Christiane, Nagelli Lakshmi V, Rosen Steven T, Kuzel Timothy M, Guitart Joan
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Expert Opin Pharmacother. 2006 May;7(7):907-15. doi: 10.1517/14656566.7.7.907.
Primary cutaneous T-cell lymphomas encompass a spectrum of non-Hodgkin's lymphomas that are characterised by clonal proliferation of skin-homing malignant T lymphocytes. Mycosis fungoides and the leukaemic variant Sézary syndrome, collectively referred to as cutaneous T-cell lymphomas, are the most common entities. No curative therapy exists and patients ultimately develop advanced or relapsed disease that is refractory to standard treatment options. Therefore, there is a great need for the development of novel emerging therapies. Bexarotene is the first synthetic nuclear retinoid X receptor-selective retinoid approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma in all stages, as both an oral capsule and a topical gel formulation. Bexarotene was found to induce apoptosis in a variety of preclinical in vitro and in vivo models including cutaneous T-cell lymphoma cells, and has shown efficacy in two multi-centre, open-label Phase II - III clinical trials for early and advanced stages of cutaneous T-cell lymphoma in patients who have failed or were refractory to standard therapies. New insights into the immunomodulatory function of bexarotene have indicated opportunities for combined treatment with IFN-alpha, denileukin diftitox or phototherapy. This article reviews the biological properties, pharmacokinetics, clinical efficacy, safety and role of bexarotene in the treatment of cutaneous T-cell lymphoma.
原发性皮肤T细胞淋巴瘤包括一系列非霍奇金淋巴瘤，其特征是皮肤归巢性恶性T淋巴细胞的克隆性增殖。蕈样肉芽肿及其白血病变体塞扎里综合征统称为皮肤T细胞淋巴瘤，是最常见的类型。目前尚无治愈性疗法，患者最终会发展为对标准治疗方案难治的晚期或复发性疾病。因此，迫切需要开发新出现的疗法。贝沙罗汀是美国食品药品监督管理局（FDA）批准的首个用于治疗各阶段难治性皮肤T细胞淋巴瘤的合成核视黄酸X受体选择性视黄酸，有口服胶囊和外用凝胶两种剂型。在包括皮肤T细胞淋巴瘤细胞在内的多种临床前体外和体内模型中，发现贝沙罗汀可诱导细胞凋亡，并且在两项针对皮肤T细胞淋巴瘤早期和晚期患者的多中心、开放标签II - III期临床试验中显示出疗效，这些患者对标准疗法无效或难治。对贝沙罗汀免疫调节功能的新见解表明了其与干扰素-α、地尼白介素-毒素或光疗联合治疗的机会。本文综述了贝沙罗汀在治疗皮肤T细胞淋巴瘤中的生物学特性、药代动力学、临床疗效、安全性及作用。
