Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma
Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma
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DOI：
10.1093/annonc/mdn031
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发表时间：
2008-05-01
影响因子：
50.5
通讯作者：
Cheson, B. D.
中科院分区：
文献类型：
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作者：
Crump, M.;Coiffier, B.;Cheson, B. D.
背景：伏立诺他在难治性皮肤T细胞淋巴瘤中表现出活性。在I期试验中，弥漫性大B细胞淋巴瘤（DLBCL）中出现了令人鼓舞的活性，患者和方法：我们进行了口服伏立诺他300 mg b.i.d. (14天/3周或3天/周）。缓解率和持续时间（DOR），进展时间（TTP）和safety进行了assessed.Results：18例患者入组（中位年龄：66岁;中位既往治疗：2）。7例接受300 mg b.i.d. 14天/3周，但4例出现3级或4级毒性（剂量限制性毒性，DLT）。将时间表修订为300 mg b.i.d.。3天/周），无一例发生DLT。1例达到完全缓解（TtR = 85天; DOR = > 468天），1例病情稳定（301天）。16例因疾病进展而停药;中位TTP为44天。中位周期数为2（1至> 19）。常见的药物相关不良事件（AE;大多数为1/2级）为腹泻、疲乏、恶心、贫血和呕吐。3例患者减量;无患者因药物相关AE停药。药物相关AE ≥ 3级包括血小板减少（16.7%）和虚弱（11.1%）。3天/周或200 mg b.i.d. 14天/3周，但对复发DLBCL的活性有限。
Background: Vorinostat has demonstrated activity in refractory cutaneous T-cell lymphoma. In a phase I trial, an encouraging activity in diffuse large-B-cell lymphoma (DLBCL) was noted.Patients and methods: We carried out a phase II trial (NCT00097929) of oral vorinostat 300 mg b.i.d. (14 days/3 weeks or 3 days/week) in patients with measurable, relapsed DLBCL who had received two or more systemic therapies. Response rate and duration (DOR), time to progression (TTP) and safety were assessed.Results: Eighteen patients were enrolled (median age: 66 years; median prior therapies: 2). Seven received 300 mg b.i.d. 14 days/3 weeks, but four had grade 3 or 4 toxicity (dose-limiting toxicity, DLT). The schedule was amended to 300 mg b.i.d. 3 days/week), and none had DLT. One achieved a complete response (TtR = 85 days; DOR = > 468 days) and one had stable disease (301 days). Sixteen discontinued for progressive disease; median TTP was 44 days. Median number of cycles was 2 (1 to > 19). Common drug-related adverse experiences (AEs; mostly grade 1/2) were diarrhea, fatigue, nausea, anemia and vomiting. Three patients had dose reduction; none discontinued for drug-related AEs. Drug-related AE >= grade 3 included thrombocytopenia (16.7%) and asthenia (11.1%).Conclusion: Vorinostat was well tolerated at 300 mg b.i.d. 3 days/week or 200 mg b.i.d. 14 days/3 weeks but had limited activity against relapsed DLBCL.