Foss Francine, Advani Ranjana, Duvic Madeleine, Hymes Kenneth B, Intragumtornchai Tanin, Lekhakula Arnuparp, Shpilberg Ofer, Lerner Adam, Belt Robert J, Jacobsen Eric D, Laurent Guy, Ben-Yehuda Dina, Beylot-Barry Marie, Hillen Uwe, Knoblauch Poul, Bhat Gajanan, Chawla Shanta, Allen Lee F, Pohlman Brad
Yale Cancer Center, New Haven, CT, USA.
Br J Haematol. 2015 Mar;168(6):811-9. doi: 10.1111/bjh.13222. Epub 2014 Nov 17.
Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed ≥1 prior systemic therapy and were treated with belinostat (1000 mg/m(2) intravenously ×5 d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n = 24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n = 29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at www.clinicaltrials.gov as NCT00274651.
贝利司他是一种具有抗肿瘤和抗血管生成特性的泛组蛋白去乙酰化酶抑制剂。一项开放标签、多中心研究纳入了外周T细胞淋巴瘤(PTCL)或皮肤T细胞淋巴瘤(CTCL)患者,这些患者既往至少接受过≥1次全身治疗且治疗失败,接受贝利司他治疗(1000 mg/m²静脉注射,每21天周期的第1至5天)。主要终点为客观缓解率(ORR)。PTCL患者(n = 24)既往接受全身治疗的中位数为3次(范围1 - 9次),40%患者为IV期疾病。CTCL患者(n = 29)既往接受皮肤定向治疗的中位数为1次(范围0 - 4次),全身治疗的中位数为4次(范围1 - 9次);55%患者为IV期疾病。ORR分别为25%(PTCL)和14%(CTCL)。77%的患者发生了治疗相关不良事件;恶心(43%)、呕吐(21%)、输注部位疼痛(13%)和头晕(11%)的发生率最高。治疗相关严重不良事件包括5级室颤;4级血小板减少;3级外周水肿、失用症、麻痹性肠梗阻和肺炎;以及2级颈静脉血栓形成。贝利司他单药治疗对复发/难治性PTCL和CTCL患者耐受性良好且有效。该试验在www.clinicaltrials.gov上注册,注册号为NCT00274651。