Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Dermatology, Takamatsu Red Cross Hospital, Takamatsu, Japan.
J Dermatol. 2019 Jul;46(7):557-563. doi: 10.1111/1346-8138.14923. Epub 2019 May 15.
The present study (B-1201 clinical trial) was conducted as a multicenter, open-label, single-arm phase II study to evaluate the long-term safety, tolerability and efficacy of bexarotene. This study enrolled 10 Japanese adults aged more than 20 years with cutaneous T-cell lymphoma (CTCL) who completed the 24-week study period of the B-1101 trial. The objective response rate (ORR) was 53.8% (95% confidence interval, 25.1-80.8). In the early stage (IB), the ORR was 60% (3/5 cases). In the advanced stage (IIB and IIIA), the ORR was 57.1% (4/7 cases). The median time to response was 58 days (range, 27-168). The median treatment duration was 380 days (range, 33-1674). The median duration of response (DOR) could not be reached during the study period. The longest DOR reached 1618 days at the end of the B-1201 trial. Nine patients (56.3%) in the full analysis set (FAS) population experienced dose reduction of bexarotene. Common drug-related adverse events in the FAS population included hypothyroidism (93.8%), hypertriglyceridemia (81.3%), hypercholesterolemia (81.3%), leukopenia (68.8%) and neutropenia (56.3%). Dose-limiting toxicity (DLT) was present in five (38.5%) of the 13 patients in the 300 mg/m cohort. Of the five patients, four developed grade 3 neutropenia and one developed grade 4 hypertriglyceridemia. All DLT cases recovered after the discontinuation of bexarotene. None of the five patients discontinued this trial because of DLT. The B-1201 trial shows the long-term safety of oral bexarotene for Japanese patients with CTCL, despite frequent dose reduction.
本研究（B-1201 临床试验）是一项多中心、开放性、单臂 II 期研究，旨在评估贝沙罗汀的长期安全性、耐受性和疗效。该研究纳入了 10 名年龄大于 20 岁的日本 CTCL 成年患者，这些患者完成了 B-1101 试验的 24 周研究周期。客观缓解率（ORR）为 53.8%（95%置信区间，25.1-80.8）。在早期（IB）阶段，ORR 为 60%（5/5 例）。在晚期（IIB 和 IIIA）阶段，ORR 为 57.1%（4/7 例）。反应的中位时间为 58 天（范围，27-168）。中位治疗持续时间为 380 天（范围，33-1674）。在研究期间，无法达到中位缓解持续时间（DOR）。最长的 DOR 在 B-1201 试验结束时达到 1618 天。在全分析集（FAS）人群中，有 9 名患者（56.3%）经历了贝沙罗汀的剂量减少。FAS 人群中常见的药物相关不良反应包括甲状腺功能减退症（93.8%）、高甘油三酯血症（81.3%）、高胆固醇血症（81.3%）、白细胞减少症（68.8%）和中性粒细胞减少症（56.3%）。在 300mg/m 队列的 13 名患者中，有 5 名（38.5%）发生剂量限制毒性（DLT）。这 5 名患者中，有 4 名发生 3 级中性粒细胞减少症，1 名发生 4 级高甘油三酯血症。所有 DLT 病例在停用贝沙罗汀后均恢复。没有 5 名患者因 DLT 而停止该试验。B-1201 试验表明，口服贝沙罗汀治疗日本 CTCL 患者具有长期安全性，尽管频繁进行剂量减少。
