Objective: This article compares the effect of interferon alfa plus cytarabine (IFN-alfa + Ara-C) versus IFN-alfa alone on the chronic phase of chronic myelogenous leukemia.
Methods: Electronic searches were performed in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese Biomedical Database, China Journal Full-text Database, and Chinese Scientific Journals Database. The languages were limited to Chinese and English. Randomized controlled trials were selected by 2 investigators. Analyses were performed using RevMan 5.0 software.
Results: A total of 3139 patients in 4 studies met the inclusion criteria. In those patients, complete hematologic response and cytogenetic responses showed significant improvements in favor of IFN-alfa + Ara-C, with complete hematologic response relative risk (RR) of 1.15 (95% CI, 1.09-1.21), complete cytogenetic response RR of 1.87 (95% CI, 1.47-2.38), partial cytogenetic response RR of 1.48 (95% CI, 1.25-1.75), and major cytogenetic response RR of 1.61 (95% CI, 1.42-1.83), respectively. The overall 3-year survival rate in the IFN-alfa + Ara-C group was 86% compared with 79% in the IFN-alfa group (RR = 1.09; 95% CI, 1.03-1.14). In the other 2 studies, 5-year overall survival was 69% compared with 63%, respectively (RR = 1.08; 95% CI, 1.01-1.15). However, IFN-alfa and Ara-C involved higher risk of hematologic toxicity, gastrointestinal adverse events, and severe mucositis compared with IFN-alfa monotherapy (RR = 2.63 [95% CI, 1.94-3.56); RR = 3.38 [95% CI, 2.28-5.00], and RR = 8.84 [95% CI, 3.82-20.46], respectively). Weight loss and skin rash were also observed more frequently in the combination treatment group (RR = 2.00 [95% CI, 1.47-2.73) and RR = 3.75 [95% CI, 2.13-6.59], respectively).
Conclusions: In patients with chronic myelogenous leukemia in the chronic phase, the combination of IFN-alfa + Ara-C demonstrated improved complete hematologic response, superior cytogenetic responses, and higher rates of 3- and 5-year survival than IFN-alfa alone. However, combination therapy is more likely to cause serious adverse effects. Well-designed studies will be required to determine the outcomes and adverse effects of the 2 drugs as treatment for patients with chronic myelogenous leukemia who cannot afford molecularly targeted drugs.
Keywords: chronic myelogenous leukemia; cytarabine; interferon alfa; meta-analysis.