Fludarabine in comparison to alkylator-based regimen as induction therapy for chronic lymphocytic leukemia: a systematic review and meta-analysis.
The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several studies but no studies have yet reported a pooled estimate of the treatment effect. We performed a systematic review of evidence from 5 randomized controlled trials involving approximately 1300 patients with CLL, comparing Fludarabine with several alkylator-based combination regimens in the primary treatment of CLL. Complete response rate was significantly higher for Fludarabine compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02), while overall response, though superior, did not reach statistical significance (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95% CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95% CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis supports the findings that Fludarabine as an induction agent for patients with CLL yields a better clinical response with acceptable toxicity when compared with alkylator-based combination therapy, but without a survival benefit by 5-6 years of follow up.
Zhu
Q
Q
Department of Hematology, Shanghai No 9 People's Hospital, Shanghai Second Medical University, Shanghai, The People's Republic of China.
Tan
D C L
DC
Samuel
M
M
Chan
E S Y
ES
Linn
Y C
YC
D000477:Alkylating Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D016239:MEDLINE; D009504:Neutrophils / Q000378:metabolism; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine