Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma
Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma
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DOI：
10.1111/cas.13340
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发表时间：
2017-10-01
期刊：
影响因子：
5.7
通讯作者：
Tobinai, Kensei
中科院分区：
文献类型：
--
作者：
Maruyama, Dai;Nagai, Hirokazu;Tobinai, Kensei
普拉曲沙是一种新型抗叶酸剂，在美国获批用于治疗复发性或难治性外周T细胞淋巴瘤。为了评估其在日本患者中的安全性、有效性和药代动力学，我们进行了一项I/II期研究。普拉曲沙每周静脉注射6周，共7周。所有患者同时接受维生素B-12和叶酸。在第一阶段，3名患者接受普拉曲沙30 mg/m2，没有出现剂量限制性毒性。在第二阶段，我们用该剂量治疗了另外22名患者。中位治疗周期数为1（范围：1-9）。20例可评价患者中有9例（45%）通过中心审查实现了客观缓解，包括2例完全缓解。所有缓解均发生在第一个治疗周期内。在数据截止时，中位无进展生存期为150天。未达到中位总生存期。在总人群中，最常报告的不良事件包括粘膜炎（88%）、血小板减少症（68%）、肝功能检查异常（64%）、贫血（60%）和淋巴细胞减少症（56%）。3/4级不良事件包括淋巴细胞减少症（52%）、血小板减少症（40%）、白细胞减少症（28%）、中性粒细胞减少症（24%）、贫血（20%）和粘膜炎（20%）。药代动力学特征显示重复给药无药物蓄积。这些结果表明，普拉曲沙在日本复发性或难治性外周T细胞淋巴瘤患者中通常耐受良好且有效。本试验在ClinicalTrials.gov（NCT 02013362）上注册。
Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6weeks of a 7-week cycle. All patients received concurrent vitamin B-12 and folic acid. In phase I, three patients received pralatrexate 30mg/m(2) and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).