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

• Published in: Blood Vol. 103; no. 12; pp. 4408 - 4415
• Main Authors: Kluin-Nelemans, Hanneke C., Buck, Georgina, le Cessie, Saskia, Richards, Sue, Beverloo, H. Berna, Falkenburg, J. H. Frederik, Littlewood, Tim, Muus, Petra, Bareford, David, van der Lelie, Hans, Green, Anthony R., Roozendaal, Klaas J., Milne, Alison E., Chapman, Claire S., Shepherd, Patricia
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.06.2004; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cause of Death; Dose-Response Relationship, Drug; Hematologic and hematopoietic diseases; Humans; Hydroxyurea - administration & dosage; Immunotherapy; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Patient Compliance; Pharmacology. Drug treatments; Placebos; Quality of Life; Survival Analysis; Alpha interferon; Low dose; Malignant hemopathy; Posology; Osteoarticular system; Myeloproliferative syndrome; Chronic; Randomization; Treatment; Immunotherapy; Chronic myelocytic leukemia; Clinical trial; High dose; Comparative study
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-10-3605

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/m2 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 × 109/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. (Blood. 2004;103:4408-4415)