Flinn Ian W, Neuberg Donna S, Grever Michael R, Dewald Gordon W, Bennett John M, Paietta Elisabeth M, Hussein Mohamad A, Appelbaum Frederick R, Larson Richard A, Moore Dennis F, Tallman Martin S
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD, USA.
J Clin Oncol. 2007 Mar 1;25(7):793-8. doi: 10.1200/JCO.2006.08.0762. Epub 2007 Feb 5.
The combination of fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing fludarabine and cyclophosphamide (FC arm) versus fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL.
Symptomatic, previously untreated patients with CLL were randomly assigned to receive either fludarabine 25 mg/m2 intravenously (IV) days 1 through 5 or cyclophosphamide 600 mg/m2 IV day 1 and fludarabine 20 mg/m2 IV days 1 through 5. These cycles were repeated every 28 days for a maximum of six cycles.
A total of 278 patients were randomly assigned in this Intergroup study. Treatment with fludarabine and cyclophosphamide was associated with a significantly higher complete response (CR) rate (23.4% v 4.6%; P < .001) and a higher overall response (OR) rate (74.3% v 59.5%, P = .013) than treatment with fludarabine as a single agent. Progression-free survival (PFS) was also superior in patients treated with fludarabine and cyclophosphamide than those treated with fludarabine (31.6 v 19.2 months, P < .0001). Fludarabine and cyclophosphamide caused additional hematologic toxicity, including more severe thrombocytopenia (P = .046), but it did not increase the number of severe infections (P = .812).
Fludarabine and cyclophosphamide produced an increase in OR and CR, and it improved PFS in patients with previously untreated CLL compared with fludarabine alone and was not associated with an increase in infectious toxicity.
氟达拉滨与环磷酰胺联合方案对慢性淋巴细胞白血病（CLL）患者是一种有效的治疗方案。然而，与单用氟达拉滨相比，其毒性可能会增加。E2997是一项III期随机组间试验，比较氟达拉滨与环磷酰胺联合方案（FC组）和单用氟达拉滨方案（F组）用于接受CLL首次化疗方案的患者。
有症状的、既往未治疗的CLL患者被随机分配，接受氟达拉滨25mg/m²静脉注射，第1至5天，或环磷酰胺600mg/m²静脉注射第1天及氟达拉滨20mg/m²静脉注射第1至5天。每28天重复这些疗程，最多6个疗程。
在这项组间研究中，共有278例患者被随机分配。与单用氟达拉滨治疗相比，氟达拉滨与环磷酰胺联合治疗的完全缓解（CR）率显著更高（23.4%对4.6%；P<.001），总缓解（OR）率也更高（74.3%对59.5%，P=.013）。接受氟达拉滨与环磷酰胺联合治疗患者的无进展生存期（PFS）也优于接受氟达拉滨治疗的患者（31.6对19.2个月，P<.0001）。氟达拉滨与环磷酰胺导致了额外的血液学毒性，包括更严重的血小板减少（P=.046），但未增加严重感染的发生率（P=.812）。
与单用氟达拉滨相比，氟达拉滨与环磷酰胺联合治疗可提高OR和CR，并改善既往未治疗的CLL患者的PFS，且不增加感染性毒性。
