title: Long-term response to imatinib is not affected by the initial dose  in patients with Philadelphia chromosome-positive chronic  myeloid leukemia in chronic phase: final update from the Tyrosine  Kinase Inhibitor Optimization and Selectivity (TOPS) study.
abstract: The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival(PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR.Adverse events were more frequent with high-dose imatinib. Patients with B1 treatment interruption (vs [1) and those able to maintain imatinib C600 mg/day (vs\600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with longterm clinical outcomes.
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Lidia
authors.initials: L
authors.lastname: Mongay
authors.forename: Manisha
authors.initials: M
authors.lastname: Mone
authors.forename: Christine-Elke
authors.initials: CE
authors.lastname: Ortmann
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl