Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial
Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial
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DOI：
10.1016/s0140-6736(10)61381-5
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发表时间：
2010-10-02
期刊：
影响因子：
168.9
通讯作者：
Stilgenbauer, S.
中科院分区：
文献类型：
--
作者：
Hallek, M.;Fischer, K.;Stilgenbauer, S.
背景在几项2期临床试验中报告的有希望的结果的基础上，我们研究了在氟达拉滨和环磷酰胺的一线化疗中加入单克隆抗体利妥昔单抗是否会改善慢性淋巴细胞白血病患者的预后。身体健康的病人年龄30-81岁的CD 20阳性慢性淋巴细胞白血病患者按1：1的比例随机分配接受6个疗程的静脉注射氟达拉滨在11个国家的190个中心，在每个28天疗程的前3天，使用或不使用利妥昔单抗（第一个疗程第0天375 mg/m2，第二至第六个疗程第1天500 mg/m2）。研究者和患者未对计算机生成的治疗分配设盲。主要终点是无进展生存期（PFS）。本研究注册于ClinicalTrials.gov，编号NCT 00281918。结果408例患者被分配到氟达拉滨、环磷酰胺和利妥昔单抗（化学免疫治疗组），409例患者被分配到氟达拉滨和环磷酰胺（化疗组）;所有患者都进行了分析。随机分组后3年，免疫化疗组65%的患者无进展，而化疗组45%的患者无进展（风险比0.56 [95%CI 0.46-0.69]，p
Background On the basis of promising results that were reported in several phase 2 trials, we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia.Methods Treatment-naive, physically fit patients (aged 30-81 years) with CD20-positive chronic lymphocytic leukaemia were randomly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days of each 28-day treatment course with or without rituximab (375 mg/m(2) on day 0 of first course, and 500 mg/m(2) on day 1 of second to sixth courses) in 190 centres in 11 countries. Investigators and patients were not masked to the computer-generated treatment assignment. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00281918.Findings 408 patients were assigned to fludarabine, cyclophosphamide, and rituximab (chemoimmunotherapy group) and 409 to fludarabine and cyclophosphamide (chemotherapy group); all patients were analysed. At 3 years after randomisation, 65% of patients in the chemoimmunotherapy group were free of progression compared with 45% in the chemotherapy group (hazard ratio 0.56 [95% CI 0.46-0.69], p