Efficacy and Safety of Clofarabine in Relapsed and/or Refractory Non-Hodgkin Lymphoma, Including Rituximab-Refractory Patients
Efficacy and Safety of Clofarabine in Relapsed and/or Refractory Non-Hodgkin Lymphoma, Including Rituximab-Refractory Patients
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DOI：
10.1002/cncr.25603
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发表时间：
2011-04-01
期刊：
影响因子：
6.2
通讯作者：
Venugopal, Parameswaran
中科院分区：
文献类型：
--
作者：
Nabhan, Chadi;Davis, Nancy;Venugopal, Parameswaran
背景技术背景：目前，对于不适合移植或在骨髓移植后失败的复发性和/或难治性非霍奇金淋巴瘤（NHL）患者没有标准疗法。本报告的作者研究了氯法拉滨（CLO）在这些患者中的安全性和有效性。方法：在一项2步、开放标签研究中，CLO（每天1小时静脉输注，持续5天）每28天给药一次（最多6个周期）。在I期部分（n = 7;标准3 + 3研究设计），剂量递增2 mg/m2，以确定最大耐受剂量（MTD）。II期研究（n = 26）以MTD开始，随访患者直至疾病进展。研究结果：在33例入组患者中，31例患者（中位年龄69岁）可评价; 24%在既往干细胞移植后失败，72%为利妥昔单抗难治性。CLO的MTD为4 mg/m2。总有效率为42%。7例患者（23%）达到完全缓解，6例患者（19%）达到部分缓解。中位缓解持续时间为5个月。在利妥昔单抗难治性患者中，总缓解率为47%（完全缓解率为28%），中位缓解持续时间为7个月。在中位随访14个月时，45%的患者仍然存活（中位总生存期为10个月）。毒性主要为血液学毒性（>= 60%的患者出现中性粒细胞减少症或血小板减少症）。非血液学毒性包括肿瘤溶解综合征、感染和肾功能不全（各占6%）。未观察到给药相关死亡。结论：单药CLO在难治性NHL患者（包括利妥昔单抗难治性亚组患者）中具有活性且耐受性良好。主要毒副反应为可逆性骨髓抑制。研究注册于www.clinicaltrials.gov（NCT 00156013）。Cancer 2011; 117：1490-7. (C)2010美国癌症协会
BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2). The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (>= 60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2011; 117: 1490-7. (C) 2010 American Cancer Society.