title: Phase IV study evaluating efficacy of escalated dose of imatinib in chronic myeloid leukemia patients showing suboptimal response to standard dose imatinib.
abstract: The aim of this phase IV study was to (1) to define efficacy of escalating dose imatinib in chronic myeloid leukemia (CML) patients showing suboptimal response to standard dose imatinib and (2) to find markers that predict the response to escalating doses of imatinib. CML patients in chronic phase (CP) who failed to achieve optimal response with 400 mg/day imatinib or patients in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of 400-600 mg/day imatinib were enrolled. CP patients received 600 mg/day, while AP/BC patients received 600-800 mg/day imatinib. Patients received imatinib for at least 12 months or until the disease progression or intolerable toxicity. Along with cytogenetic response (CyR), molecular response was assessed with BCR-ABL/ABL ratio. Baseline BCR-ABL gene mutation test was performed. Seventy-one patients (median age, 49.0 years, M:F = 50:21) received escalated dose imatinib. Grade 3 edema in two patients was the only nonhematologic toxicities more than grade 2. For evaluable patients, 30.8% of patients achieved CCyR at 6 months, and median time to treatment failure (TTFx) was 18.0 months. TTFx was longer in patients who achieved greater than 50% reduction in BCR-ABL/ABL within 6 months (early molecular responder (EMR)) compared with those who did not (non-EMR; p < 0.001). Of 31 patients who had mutational status data, three had mutation. All mutants failed to achieve CCyR. In conclusion, escalated dose imatinib shows considerable efficacy with tolerable toxicity in CML patients showing suboptimal response to standard dose imatinib. EMR is an early predictive marker for positive imatinib response.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Byoung Kook
authors.initials: BK
authors.lastname: Kim
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Park
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Young Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jooseop
authors.initials: J
authors.lastname: Chung
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Hong Suk
authors.initials: HS
authors.lastname: Song
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000378:metabolism; D001752:Blast Crisis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl