Maruyama Dai, Tobinai Kensei, Ogura Michinori, Uchida Toshiki, Hatake Kiyohiko, Taniwaki Masafumi, Ando Kiyoshi, Tsukasaki Kunihiro, Ishida Takashi, Kobayashi Naoki, Ishizawa Kenichi, Tatsumi Yoichi, Kato Koji, Kiguchi Toru, Ikezoe Takayuki, Laille Eric, Ro Tokihiro, Tamakoshi Hiromi, Sakurai Sanae, Ohtsu Tomoko
Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.
Department of Hematology, Tokai Central Hospital, Gifu, Japan.
Int J Hematol. 2017 Nov;106(5):655-665. doi: 10.1007/s12185-017-2286-1. Epub 2017 Jun 29.
This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ≥20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m. The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively. Intent-to-treat patients were those who received ≥1 romidepsin dose (PTCL, n = 48; CTCL, n = 2). In phase I, none of the patients (n = 3, 9 mg/m; n = 6, 14 mg/m) exhibited DLT. In phase II, 40 patients with PTCL were treated with 14 mg/m romidepsin. The most common treatment-emergent grade ≥3 adverse events were lymphopenia (74%), neutropenia (54%), leukopenia (46%), and thrombocytopenia (38%). Patients in phase II showed a 43% ORR, including 25% complete responses. Median progression-free survival was 5.6 months and median duration of response was 11.1 months. This phase I/II study identified a well-tolerated dose of romidepsin, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with relapsed/refractory PTCL. ClinicalTrials.gov Identifier NCT01456039.
这项I/II期多中心研究评估了罗米地辛治疗日本复发/难治性外周T细胞淋巴瘤（PTCL）或皮肤T细胞淋巴瘤（CTCL）患者的疗效。年龄≥20岁的患者在每28天周期的第1、8和15天接受4小时静脉输注罗米地辛。I期采用3+3设计确定罗米地辛9和14mg/m方案的任何剂量限制性毒性（DLT）。I期和II期的主要终点分别是DLT和总缓解率（ORR）。意向性治疗患者是那些接受≥1剂罗米地辛的患者（PTCL，n = 48；CTCL，n = 2）。在I期，没有患者（n = 3，9mg/m；n = 6，14mg/m）出现DLT。在II期，40例PTCL患者接受14mg/m罗米地辛治疗。最常见的≥3级治疗中出现的不良事件是淋巴细胞减少（74%）、中性粒细胞减少（54%）、白细胞减少（46%）和血小板减少（38%）。II期患者的ORR为43%，包括25%的完全缓解。中位无进展生存期为5.6个月，中位缓解持续时间为11.1个月。这项I/II期研究确定了罗米地辛的一个耐受性良好的剂量，其毒性特征可接受，对日本复发/难治性PTCL患者具有临床意义的疗效。ClinicalTrials.gov标识符NCT01456039。
