title: Randomized comparison of low-dose versus high-dose interferon-alfa in chronic myeloid leukemia: prospective collaboration of 3 joint trials by the MRC and HOVON groups.
abstract: The optimal dose of interferon-alfa (IFN) for chronic myeloid leukemia (CML) is unknown. Retrospective analyses suggest that low doses are as effective as high doses, with less toxicity and fewer patients abandoning the drug. The Dutch Hemato-Oncology Association (HOVON) and British Medical Research Council (MRC) cooperative groups jointly performed randomized trials in newly diagnosed CML patients, comparing high-dose IFN (5 MIU/m(2) daily) with low-dose (3 MIU, 5 times a week). Both arms allowed additional hydroxyurea to keep the white blood cell count lower than 5 x 10(9)/L. Quality of life data were collected in a subset of patients. Between 1993 and 2001, 407 patients were randomized. At a median follow-up of 53 months, there were no significant differences in overall survival (odds ratio = 1.09, 95% confidence interval, 0.81-1.46), progression-free survival, and complete hematologic or major cytogenetic responses. Fewer patients in the low-dose group abandoned IFN for reasons other than transplant or progressive disease (P =.002, 58% vs 72% at 5 years). Quality of life data showed comparable results in both arms for most factors. There is no evidence of benefit for high-dose IFN compared with low-dose for the treatment of CML. Therefore, when IFN is combined with other drugs, low-dose IFN is advised, to minimize toxicity and costs.
authors.affiliation: Department of Haematology, Western General Hospital, Edinburgh, Scotland EH4 2XU, UK.
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: Georgina
authors.initials: G
authors.lastname: Buck
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Sue
authors.initials: S
authors.lastname: Richards
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Tim
authors.initials: T
authors.lastname: Littlewood
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: David
authors.initials: D
authors.lastname: Bareford
authors.forename: Hans
authors.initials: H
authors.lastname: van der Lelie
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Roozendaal
authors.forename: Alison E
authors.initials: AE
authors.lastname: Milne
authors.forename: Claire S
authors.initials: CS
authors.lastname: Chapman
authors.forename: Patricia
authors.initials: P
authors.lastname: Shepherd
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002423:Cause of Death; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010349:Patient Compliance; D010919:Placebos; D011788:Quality of Life; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D010919:Placebos; D006918:Hydroxyurea