title: Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase.
abstract: BACKGROUND
  Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown.
  
  
  METHODS
  We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 3 weeks.
  
  
  RESULTS
  The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities.
  
  
  CONCLUSIONS
  Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: David
authors.initials: D
authors.lastname: McConkey
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D001549:Benzamides; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D004351:Drug Resistance; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D001897:Boronic Acids; D010879:Piperazines; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D011743:Pyrimidines; D000069286:Bortezomib; D000068877:Imatinib Mesylate