Keating Michael J, O'Brien Susan, Albitar Maher, Lerner Susan, Plunkett William, Giles Francis, Andreeff Michael, Cortes Jorge, Faderl Stefan, Thomas Deborah, Koller Charles, Wierda William, Detry Michelle A, Lynn Alice, Kantarjian Hagop
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA.
J Clin Oncol. 2005 Jun 20;23(18):4079-88. doi: 10.1200/JCO.2005.12.051. Epub 2005 Mar 14.
Fludarabine and cyclophosphamide (FC), which are active in treatment of chronic lymphocytic leukemia (CLL), are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines. A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >/= 50%.
We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL. Flow cytometry was used to measure residual disease. Results and safety were compared with a previous regimen using FC.
The median age was 58 years; 75 patients (33%) had Rai stage III to IV disease. The CR rate was 70% (95% CI, 63% to 76%), the nodular partial remission rate was 10%, and the partial remission rate was 15%, for an overall response rate of 95% (95% CI, 92% to 98%). Two thirds of patients evaluated with flow cytometry had less than 1% CD5- and CD19-coexpressing cells in bone marrow after therapy. Grade 3 to 4 neutropenia occurred during 52% of courses; major and minor infections were seen in 2.6% and 10% of courses, respectively. One third of the 224 patients had >/= one episode of infection, and 10% had a fever of unknown origin.
FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69% of patients were projected to be failure free at 4 years (95% CI, 57% to 81%).
氟达拉滨和环磷酰胺（FC）对慢性淋巴细胞白血病（CLL）治疗有效，在体外对淋巴瘤细胞系而言，它们与单克隆抗体利妥昔单抗具有协同作用。制定了一个由氟达拉滨、环磷酰胺和利妥昔单抗（FCR）组成的化学免疫治疗方案，目标是将既往未治疗的CLL患者的完全缓解（CR）率提高至≥50%。
我们对224例进展期或晚期CLL患者进行了一项单臂研究，以FCR作为初始治疗。采用流式细胞术检测残留疾病。将结果和安全性与先前使用FC的方案进行比较。
中位年龄为58岁；75例患者（33%）处于Rai分期III至IV期疾病。CR率为70%（95%CI，63%至76%），结节性部分缓解率为10%，部分缓解率为15%，总缓解率为95%（95%CI，92%至98%）。三分之二接受流式细胞术评估的患者在治疗后骨髓中CD5和CD19共表达细胞少于1%。52%的疗程中出现3至4级中性粒细胞减少；分别有2.6%和10%的疗程出现严重和轻度感染。224例患者中有三分之一发生≥1次感染，10%有不明原因发热。
FCR在既往未治疗的CLL中产生了较高的CR率。大多数患者在治疗结束时通过流式细胞术检测不到疾病。治疗失败时间分析显示，预计69%的患者在4年时无失败（95%CI，57%至81%）。
