PURPOSE The histone deacetylase (HDAC) inhibitor romidepsin and the anthracycline liposomal doxorubicin (LD) have modest single-agent activity in cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). We investigated the safety and efficacy of the combination of these two agents in CTCL and PTCL. PATIENTS AND METHODS Using CTCL cell lines and primary CTCL tumor cells, we demonstrated synergistic antitumor activity with romidepsin plus doxorubicin. We then conducted a phase I dose-escalation study of the romidepsin/LD combination in relapsed/refractory CTCL and PTCL. The primary objective was to determine the MTD of romidepsin in combination with LD at 20 mg/m2 i.v., once every 28 days. RESULTS Eleven patients with CTCL and 12 patients with PTCL were treated. The MTD of romidepsin was determined to be 12 mg/m2. Grade 3/4 hematologic toxicities included thrombocytopenia (17%), anemia (13%), and neutropenia (9%). The most frequent treatment-related nonhematologic adverse events were fatigue (48%), nausea (48%), vomiting (35%), and anorexia (30%). Among 21 evaluable patients, the overall response rate was 70% [1 complete response (CR), 6 partial responses (PR)] in CTCL and 27% (3 CR, 0 PR) in PTCL. Of the patients with CTCL, 8 of 10 had skin response, including 6 patients (60%) achieving skin involvement less than 10% of their body surface area at time of best response. CONCLUSIONS Romidepsin plus LD demonstrated an acceptable safety profile and promising clinical efficacy with deep skin responses in relapsed/refractory CTCL. Thus, this combination could be considered as a bridge to skin-directed treatment or allogeneic hematopoietic cell transplantation in patients with aggressive CTCL.

中文翻译：

---

罗米地辛加脂质体多柔比星对复发或难治性 T 细胞淋巴瘤患者安全有效：I 期剂量递增研究结果。

目的 组蛋白去乙酰化酶 (HDAC) 抑制剂罗米地辛和蒽环类脂质体多柔比星 (LD) 在皮肤 T 细胞淋巴瘤 (CTCL) 和外周 T 细胞淋巴瘤 (PTCL) 中具有适度的单药活性。我们研究了这两种药物在 CTCL 和 PTCL 中联合使用的安全性和有效性。患者和方法 使用 CTCL 细胞系和原发性 CTCL 肿瘤细胞，我们证明了与罗米地辛加多柔比星的协同抗肿瘤活性。然后，我们对复发/难治性 CTCL 和 PTCL 中的罗米地辛/LD 组合进行了 I 期剂量递增研究。主要目标是确定 romidepsin 与 LD 组合的 20 mg/m2 iv 的 MTD，每 28 天一次。结果 11 例 CTCL 患者和 12 例 PTCL 患者接受了治疗。确定罗米地辛的 MTD 为 12 mg/m2。3/4 级血液学毒性包括血小板减少 (17%)、贫血 (13%) 和中性粒细胞减少 (9%)。最常见的与治疗相关的非血液学不良事件是疲劳（48%）、恶心（48%）、呕吐（35%）和厌食（30%）。在 21 名可评估患者中，CTCL 的总缓解率为 70% [1 完全缓解 (CR)，6 部分缓解 (PR)]，PTCL 为 27% (3 CR，0 PR)。在 CTCL 患者中，10 名患者中有 8 名有皮肤反应，其中 6 名患者 (60%) 在最佳反应时皮肤受累面积小于其体表面积的 10%。结论 罗米地辛加 LD 在复发/难治性 CTCL 中表现出可接受的安全性和对深部皮肤反应的有希望的临床疗效。因此，