title: High-dose imatinib for newly diagnosed chronic phase chronic myeloid leukemia patients--systematic review and meta-analysis.
abstract: Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP-CML). We conducted a systematic review and meta-analysis of randomized controlled trials comparing frontline treatment with imatinib 400 mg daily versus higher doses (≥600 mg daily) in patients with CP-CML. The search yielded four trials, randomizing 1,673 patients. At 12 months, high dose compared with standard dose imatinib improved complete cytogenetic response (CCyR) (RR 1.17, 95% CI 1.08-1.26, four trials, I(2) = 33%) as well as major molecular response (MMolR) (RR 1.26, 95% CI 1.12-1.42, four trials, I(2) = 0%). There was no difference in all-cause mortality or disease progression at the end of follow up. Adverse events requiring discontinuation were more common in the high-dose arm (RR 1.98, 95% CI 1.20-3.26, three trials, I(2) = 0%), as were Grade III/IV neutropenia and thrombocytopenia: RR 1.56, 95% CI 1.15-2.12 and RR 1.86, 95% CI 1.28-2.70, respectively. There is currently insufficient evidence to support the routine use of higher doses of imatinib as frontline treatment for CP-CML. Extended follow up is needed to evaluate if the superior CCyR and MMolR with higher doses of imatinib will translate to long-term clinical benefit.
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Gafter-Gvili
authors.forename: Avi
authors.initials: A
authors.lastname: Leader
authors.forename: Ronit
authors.initials: R
authors.lastname: Gurion
authors.forename: Liat
authors.initials: L
authors.lastname: Vidal
authors.forename: Ron
authors.initials: R
authors.lastname: Ram
authors.forename: Adi
authors.initials: A
authors.lastname: Shacham-Abulafia
authors.forename: Isaac
authors.initials: I
authors.lastname: Ben-Bassat
authors.forename: Michael
authors.initials: M
authors.lastname: Lishner
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate