title: Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy.
abstract: We assessed the long-term efficacy of imatinib dose escalation in 84 patients with chronic myeloid leukemia in chronic phase who met the criteria of failure to standard-dose imatinib. Twenty-one patients with hematologic failure and 63 with cytogenetic failure had their imatinib dose escalated from 400 to 800 mg daily (n = 72) or from 300 to 600 mg daily (n = 12). After a median follow-up of 61 months from dose escalation, 69% remained alive. Complete cytogenetic responses were achieved in 40%; including 52% of patients with cytogenetic failure and 5% of those with hematologic failure. The estimated 2- and 3-year event-free survival and overall survival rates were 57% and 47%, and 84% and 76%, respectively. Responses were long-lasting; 88% of patients with major cytogenetic response sustained their response beyond 2 years. Treatment was well tolerated, with 76% of patients, at 12 months, continuing to receive imatinib at 100% of the intended dose. In conclusion, imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic failure and a previous cytogenetic response to standard-dose imatinib.
authors.affiliation: Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Jenny
authors.initials: J
authors.lastname: Shan
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Neeli
authors.initials: N
authors.lastname: Reddy
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl