Rai K R, Peterson B L, Appelbaum F R, Kolitz J, Elias L, Shepherd L, Hines J, Threatte G A, Larson R A, Cheson B D, Schiffer C A
Cancer and Leukemia Group B, Chicago, USA.
N Engl J Med. 2000 Dec 14;343(24):1750-7. doi: 10.1056/NEJM200012143432402.
Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia.
Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body-surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter every 28 days). Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles.
Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens.
When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.
氟达拉滨是一种治疗对苯丁酸氮芥初始治疗无反应的慢性淋巴细胞白血病的有效药物。我们比较了氟达拉滨与苯丁酸氮芥在慢性淋巴细胞白血病初始治疗中的疗效。
1990年至1994年期间，我们将509例既往未接受治疗的慢性淋巴细胞白血病患者随机分配至以下治疗组之一：氟达拉滨（每平方米体表面积25mg，每28天静脉滴注5天）、苯丁酸氮芥（每平方米40mg，每28天口服一次）或氟达拉滨（每平方米每天20mg，每28天静脉滴注5天）加苯丁酸氮芥（每平方米20mg，每28天口服一次）。在每月评估中出现额外缓解的患者继续接受指定治疗，最多12个周期。
当一项计划中的中期分析显示毒性过大且缓解率并不优于单用氟达拉滨时，将患者分配至氟达拉滨加苯丁酸氮芥组的工作停止。在其他两组中，单用氟达拉滨的缓解率显著高于单用苯丁酸氮芥。在170例接受氟达拉滨治疗的患者中，20%达到完全缓解，43%达到部分缓解。181例接受苯丁酸氮芥治疗的患者的相应数值分别为4%和33%（两项比较P均<0.001）。氟达拉滨组的中位缓解持续时间和中位无进展生存期分别为25个月和20个月，而苯丁酸氮芥组的这两个数值均为14个月（两项比较P均<0.001）。接受氟达拉滨治疗的患者的中位总生存期为66个月，与其他两组的总生存期无显著差异（苯丁酸氮芥组为56个月，联合治疗组为55个月）。氟达拉滨组严重感染和中性粒细胞减少症的发生率高于苯丁酸氮芥组（P=0.08），不过总体而言，两种单药治疗方案的毒性均可耐受。
当用作慢性淋巴细胞白血病的初始治疗时，氟达拉滨比苯丁酸氮芥产生更高的缓解率、更长的缓解持续时间和无进展生存期。
