Manchester Academic Health Science Centre, Institute of Cancer Sciences, University of Manchester, The Christie, Wilmslow Road, Manchester, M20 4BX, UK.
Br J Cancer. 2013 Nov 12;109(10):2566-73. doi: 10.1038/bjc.2013.616. Epub 2013 Oct 17.
Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study.
Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity.
The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months.
The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent.
吉西他滨和贝沙罗汀均为治疗皮肤 T 细胞淋巴瘤（CTCL）的既定单药。我们研究了在单臂 II 期研究中联合使用这两种药物的可行性和疗效。
对已接受标准皮肤靶向治疗且至少接受过一次系统治疗的 CTCL 患者，给予吉西他滨联合贝沙罗汀治疗，共 4 个周期，12 周为一个疗程。缓解者继续接受贝沙罗汀维持治疗，直至疾病进展或出现不可耐受的毒性。
中位年龄为 65 岁，IB 期（n=5）、IIA 期（n=2）、IIB 期（n=8）、III 期（n=8）和 IVA 期（n=12）各有 1 例；17 例患者为红皮病型，17 例患者为 B1 型，10 例患者同时为红皮病型和 B1 型。共有 30 例（86%）患者完成了 4 个周期的吉西他滨治疗。所有患者的改良严重程度加权评估工具（mSWAT）评分均有下降，尽管 12 周时的客观疾病缓解率为 31%（部分缓解（PR）31%），24 周时为 14%（PR 14%，疾病稳定（SD）23%，疾病进展（PD）54%，无法评估 9%）。中位无进展生存期为 5.3 个月，中位总生存期为 21.2 个月。
该联合方案的总体缓解率未达到进一步研究的既定目标，且低于之前报道的吉西他滨单药治疗的缓解率。
