title: A randomized study of interferon-alpha versus interferon-alpha and low-dose arabinosyl cytosine in chronic myeloid leukemia.
abstract: Interferon-alpha (IFN-alpha) has significantly prolonged survival in chronic myeloid leukemia (CML), but some patients do not respond and many responses are not durable. To improve the results, IFN-alpha has been combined with other treatments, but so far only the association with low-dose arabinosyl cytosine (LDAC) has been shown to increase the response rate and to prolong survival. Here are reported the results of a study of 538 Philadelphia chromosome-positive CML patients who were assigned at random to treatment with IFN-alpha 2a alone or in combination with LDAC. The scheduled dose of IFN-alpha 2a was 5(6) IU/m(2)/d. The scheduled dose of AC was 40 mg/d for the first 10 days of each month of treatment. The efficacy endpoints were a complete hematologic response rate at 6 months (62% in the IFN-alpha-plus-LDAC arm versus 55% in the IFN-alpha arm; P =.11), major cytogenetic response (MCgR) rate at 24 months (28% versus 18%; P =.003), and overall survival (5-year survival, 68% versus 65%; P =.77). Treatment did not affect overall survival within different prognostic risk groups: low, intermediate, or high. Also the duration of MCgR was identical. The results of this study confirm the results of a similar French study only for the response rate, not for survival, suggesting that the relationship between cytogenetic response and survival may be extremely variable and that a meta-analysis of these and other studies of IFN-alpha versus IFN-alpha plus LDAC is required to settle the issue of the role of LDAC in the treatment of CML.
authors.affiliation: L. and A. Seràgnoli Institute of Hematology and Medical Oncology, S. Orsola Hospital, University of Bologna, Italy. baccarani@med.unibo.it
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Antonio
authors.initials: A
authors.lastname: de Vivo
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Marilina
authors.initials: M
authors.lastname: Amabile
authors.forename: Mauro
authors.initials: M
authors.lastname: Fiacchini
authors.forename: Enrico
authors.initials: E
authors.lastname: Montefusco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D003561:Cytarabine