title: Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia.
abstract: The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukaemia (CP-CML) is 400 mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematological and cytogenetic response to IM400 vs. imatinib 400 mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P = 0·038; 3-log reduction: 53% vs. 35%, P = 0·049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2·9-fold lower than in the IM400 arm (P = 0·010). Complete haematological response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P = 0·040). Grade 3-4 toxicities were more common for IM800 (58% vs. 31%, P = 0·0007), and were most commonly haematological. Few patients have relapsed, progressed or died, but both progression-free (P = 0·048) and relapse-free (P = 0·031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper MRs than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity.
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Deininger
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Peter D
authors.initials: PD
authors.lastname: Emanuel
authors.forename: Martin
authors.initials: M
authors.lastname: Tallman
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D060828:Induction Chemotherapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; chronic myeloid leukaemia; imatinib