Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Viale Pio X, 88100 Catanzaro, Italy.
Expert Rev Anticancer Ther. 2011 Sep;11(9):1333-40. doi: 10.1586/era.11.118.
Until now, no approach that is able to improve overall survival of chronic lymphocytic leukemia (CLL) patients has been available. In the German CLL Study Group (GCLLSG) CLL8 trial, treatment-naive, physically fit patients (aged 30-81 years) with CD20(+) CLL 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). The two groups were well balanced with respect to baseline characteristics. The study was stopped at the preplanned interim analysis owing to an advantage in the median progression-free survival in the chemoimmunotherapy arm (51.8 vs 32.8 months; hazard ratio: 0.56; 95% CI: 0.46-0.69; p < 0.0001). Furthermore, at 3 years after randomization, 87% of patients in the chemoimmunotherapy group were alive compared with 83% in the chemotherapy group (hazard ratio: 0.67; 95% CI: 0.48-0.92; p = 0.01). In terms of toxicity, chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (p < 0.0001). There were eight (2%) treatment related-deaths in the chemoimmunotherapy arm compared with ten (3%) in the chemotherapy arm. The CLL8 trial has demonstrated that an association of rituximab, fludarabine and cyclophosphamide is effective in prolonging progression-free survival and overall survival of patients with symptomatic CLL, therefore establishing the new standard of treatment for physically fit patients.
到目前为止，还没有任何方法能够提高慢性淋巴细胞白血病（CLL）患者的总生存率。在德国 CLL 研究小组（GCLLSG）的 CLL8 试验中，身体状况良好的初治 CD20(+) CLL 患者（年龄 30-81 岁）被随机分为两组，以 1:1 的比例接受六轮静脉注射氟达拉滨（每天 25mg/m(2)）和环磷酰胺（每天 250mg/m(2)），每 28 天为一个疗程，第 1 天和第 2-6 天分别给予利妥昔单抗（第 1 疗程第 0 天 375mg/m(2)，第 2-6 疗程第 1 天 500mg/m(2)）或不给予利妥昔单抗。两组患者在基线特征方面具有良好的可比性。由于化疗免疫组的中位无进展生存期有优势，该研究在预先计划的中期分析时提前终止（51.8 与 32.8 个月；风险比：0.56；95%置信区间：0.46-0.69；p < 0.0001）。此外，随机分组 3 年后，化疗免疫组 87%的患者存活，而化疗组为 83%（风险比：0.67；95%置信区间：0.48-0.92；p = 0.01）。在毒性方面，化疗免疫组更常出现 3 级和 4 级中性粒细胞减少症（p < 0.0001）。化疗免疫组有 8 例（2%）与治疗相关的死亡，化疗组有 10 例（3%）。CLL8 试验表明，利妥昔单抗、氟达拉滨和环磷酰胺联合使用可有效延长有症状 CLL 患者的无进展生存期和总生存期，从而为身体状况良好的患者确立了新的治疗标准。
