Division of Biological Oncology Products, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Building 22, Room 5223, Silver Spring, Maryland 20993, USA.
Oncologist. 2011;16(1):97-104. doi: 10.1634/theoncologist.2010-0306. Epub 2011 Jan 6.
To describe the clinical studies that led to the FDA approval of rituximab in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with chronic lymphocytic leukemia (CLL).
The results of two multinational, randomized trials in CLL patients comparing rituximab combined with fludarabine and cyclophosphamide versus FC were reviewed. The primary endpoint of both studies was progression-free survival (PFS).
The addition of rituximab to FC decreased the risk of a PFS event by 44% in 817 previously untreated patients and by 24% in 552 previously treated patients. Median survival times could not be estimated. Exploratory analysis in patients older than 70 suggested that there was no benefit to patients when rituximab was added to FC. The safety profile observed in both trials was consistent with the known toxicity profile of rituximab, FC, or CLL.
On the basis of the demonstration of clinically meaningful prolongation of PFS, the FDA granted regular approval to rituximab in combination with FC for the treatment of patients with CLL. The magnitude of the treatment effect in patients 70 years and older is uncertain.
描述导致 FDA 批准利妥昔单抗联合氟达拉滨和环磷酰胺（FC）用于治疗慢性淋巴细胞白血病（CLL）患者的临床研究。
回顾了两项比较利妥昔单抗联合氟达拉滨和环磷酰胺与 FC 治疗 CLL 患者的多中心、随机试验的结果。这两项研究的主要终点均为无进展生存期（PFS）。
在 817 例未经治疗的患者和 552 例既往治疗的患者中，利妥昔单抗联合 FC 降低了 PFS 事件的风险，分别为 44%和 24%。无法估计中位生存时间。对年龄大于 70 岁的患者进行的探索性分析表明，当利妥昔单抗联合 FC 时，患者没有获益。两项试验中观察到的安全性特征与利妥昔单抗、FC 或 CLL 的已知毒性特征一致。
基于 PFS 临床意义的延长，FDA 批准利妥昔单抗联合 FC 用于治疗 CLL 患者。70 岁及以上患者的治疗效果大小尚不确定。
