INTERFERON-ALFA VERSUS CHEMOTHERAPY FOR CHRONIC MYELOID-LEUKEMIA - A METAANALYSIS OF 7 RANDOMIZED TRIALS

Background: Several randomized clinical trials in chronic myeloid leuk emia (CML) have reported better patient survival with interferon alfa (IFN alpha) than with standard chemotherapeutic agents, such as busulf an or hydroxyurea. However, the size and persistence of this survival benefit is uncertain, Our aim was to assess these reliably, both overa ll and in particular patient subgroups, Methods: We collaborated in a worldwide overview of all clinical trials in which patients with CML w ere randomly assigned to receive either IFN alpha as the main drug or standard chemotherapy, Trials were identified by electronic and hand s earching of the medical literature and databases and by personal conta ct, Individual patient data were available for each of 1554 patients w ho had been randomly assigned to treatment in seven trials (German, It alian, British, French, Japanese, and ''Benelux''), Intention-to-treat stratified logrank survival analyses were performed, reporting two-si ded P values, Results: Almost all of the patients in these trials had disease with the Philadelphia chromosome abnormality. Among those who did, the regimens that involved IFN alpha produced a statistically sig nificantly better survival than those involving either hydroxyurea (P = .001) or busulfan (P = .00007) alone, The 5-year survival rates were 57% with IFN alpha and 42% with chemotherapy, with an absolute differ ence of 15% (standard deviation = 3%; P<.00001), There were no trials or subgroups of patients in which the treatment difference was statist ically significantly different from the average. Conclusion: For patie nts with Philadelphia chromosome-positive chronic myeloid leukemia, th e inclusion of IFN alpha the therapeutic regimen produced substantiall y better 5-year survival than standard chemotherapy alone.