Fludarabine and bendamustine in refractory and relapsed indolent lymphoma -: a multicenter phase I/II trial of the East German society of Hematology and Oncology (OSHO)
Fludarabine and bendamustine in refractory and relapsed indolent lymphoma -: a multicenter phase I/II trial of the East German society of Hematology and Oncology (OSHO)
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DOI：
10.1080/1042819042000223822
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发表时间：
2004-09-01
影响因子：
2.6
通讯作者：
Franke, A
中科院分区：
文献类型：
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作者：
Koenigsmann, M;Knauf, WU;Franke, A
复发性或难治性惰性淋巴瘤患者的治疗依赖于新药物组合的开发。药物苯达莫司汀和氟达拉滨作为单一疗法在惰性淋巴瘤中具有细胞毒活性，并且在体外显示出协同作用。在这项研究中，我们在多中心临床I/II期试验中联合使用这两种药物，以评估其毒性和疗效。苯达莫司汀以30或40 mg/m2/ d（剂量水平1和2）给药。乌达拉滨30 mg/m2/d，每种药物在第1 - 3天给药。每4周给药6个周期。共有29例复发性或难治性惰性淋巴瘤患者纳入本研究。在I期，9例患者接受剂量水平1治疗，7例患者接受剂量水平2治疗。在II期研究中增加了13例患者。滤泡性淋巴瘤14例，套细胞性淋巴瘤11例，淋巴浆细胞性淋巴瘤2例，淋巴结边缘区淋巴瘤2例。中位年龄为62岁（范围39 - 74岁）。所有患者均处于疾病的III期或IV期，既往接受过化疗，伴或不伴额外的放射或免疫治疗。所有病例的剂量限制性毒性均为血液毒性，在剂量水平I和剂量水平2时，分别有3/7例和3/7例可评价患者发生。剂量水平2的1例患者死于中性粒细胞减少伴持续性血小板减少的败血症。研究在剂量水平1（II期）继续进行。对19例接受剂量水平1治疗的可评价患者的分析显示，47%的患者出现CTC III级血液毒性，26%的患者出现IV级血液毒性。中性粒细胞减少性发热4例（21%）。在意向治疗基础上，剂量水平1的所有患者中分别有45%或32%达到CR或PR。9例套细胞淋巴瘤患者中有9例对治疗有反应。总有效率为77%。15名应答者中有8名在中位随访时间14个月（范围2 - 43）后复发。的主要并发症。乌达拉滨与苯达莫司汀组合是血液毒性的。剂量水平1，30 mg/m2/d的两种药物在第1至3天被定义为推荐剂量。尽管预后不良（组织学亚型、疾病分期、治疗前），但该方案的缓解率良好。
The therapy of patients with relapsed or refractory indolent lymphoma relies on the development of new drug combinations. The drugs bendamustine and fludarabine have cytotoxic activity as monotherapy in indolent lymphoma and show synergism in vitro. In this study, we combined both drugs in a multicenter clinical phase I/II trial to evaluate their toxicity and efficacy. Bendamustine was given at 30 or 40 mg/m(2)/ d (dose levels 1 and 2),. udarabine at 30 mg/m(2)/d, each drug on days 1 to 3. Six cycles were to be given every 4 weeks. A total of 29 patients with relapsed or refractory indolent lymphoma were included in the study. During phase I, 9 patients were treated at dose level 1 and 7 patients at dose level 2. Thirteen patients were added to the study during phase II. Fourteen patients had follicular lymphoma, 11 patients mantle cell lymphoma, 2 patients lymphoplasmocytic and 2 patients nodal marginal zone lymphoma. Median age was 62 years ( range 39 - 74). All patients were in stages III or IV of their disease and had received prior chemotherapy with or without additional radioor immunotherapy. The dose limiting toxicity was hematotoxicity in all cases and occurred in 3 of 7 evaluable patients at dose level I and in 3 of 7 patients at dose level 2. One patient at dose level 2 died of sepsis in neutropenia with persistent thrombocytopenia. The study was continued at dose level 1 ( phase II). Analysis of 19 evaluable patients treated at dose level 1 reveiled hematotoxicity CTC grade III in 47% and grade IV in 26%. Neutropenic fever occurred in 4 patients (21%). On an intent-to-treat basis, 45% or 32% of all patients at dose level 1 reached CR or PR, respectively. Nine of 9 patients with mantle cell lymphoma responded to therapy. The overall response rate was 77%. Eight of 15 responders relapsed after a median follow-up time of 14 months ( range 2 - 43). The major complication of. udarabine in combination with bendamustine is hematotoxicity. Dose level 1 with 30 mg/m(2)/d of both drugs on days 1 to 3 was defined as the recommended dose. Despite unfavorable prognostic features ( histologic subtype, stage of disease, pretreatment) response rates were good with this regimen.