title: Imatinib front-line therapy is safe and effective in patients with chronic myelogenous leukemia with pre-existing liver and/or renal dysfunction.
abstract: BACKGROUND
  Imatinib 400 mg daily is the standard treatment for patients with chronic myelogenous leukemia (CML). The safety and efficacy of imatinib in CML patients with pre-existing liver and/or renal dysfunction has not been analyzed.
  
  
  METHODS
  The authors analyzed the outcome of 259 patients with early chronic phase CML treated with imatinib (starting dose 400 mg in 50, 800 mg in 209). Pre-existing liver and/or renal dysfunction was seen in 38 (15%) and 11 (4%) patients, respectively.
  
  
  RESULTS
  Dose reductions were required in 91 (43%) of 210 patients with normal organ function, compared with 8 (73%) of 11 (P = .065) with renal dysfunction, and 19 (50%) of 38 (P = .271) with liver dysfunction. Grade 3-4 hematologic toxicities including anemia (29%, 10%, and 7% of patients with renal dysfunction, liver dysfunction, and normal organ function, respectively), neutropenia (57%, 30%, and 30%), and thrombocytopenia (43%, 30%, and 26%) were more frequent in patients with pre-existing renal dysfunction treated with high-dose imatinib. Grade 3-4 nonhematologic toxicities were observed at similar frequencies. Complete cytogenetic response rates, event-free survival, and overall survival were similar in all groups.
  
  
  CONCLUSIONS
  Although patients with pre-existing liver and/or renal dysfunction might have a higher rate of hematologic toxicity and require more frequent dose reductions, most patients can be adequately managed, resulting in response rates and survival similar to those without pre-existing organ dysfunction.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Tong
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
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 / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007674:Kidney Diseases / Q000150:complications* / Q000503:physiopathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D008107:Liver Diseases / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate