title: Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate.
abstract: OBJECTIVE
  On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval.
  
  
  METHODS
  Four single-arm multicenter studies supported the efficacy and safety of dasatinib. The primary efficacy end point in chronic phase CML was major cytogenetic response. The primary end point in accelerated phase, myeloid phase, and lymphoid blast phase CML, and Ph(+) ALL was major hematologic response.
  
  
  RESULTS
  The four studies combined enrolled 445 patients. In patients with chronic phase CML, the major cytogenetic response rate was 45% with a complete cytogenetic response rate of 33%. Major hematologic response rates in patients with accelerated phase CML, myeloid CML, lymphoid blast CML, and Ph(+) ALL were 59%, 32%, 31%, and 42%, respectively. Median response durations in chronic phase, accelerated phase, and myeloid phase CML had not been reached. The median durations of major hematologic response were 3.7 months in lymphoid blast CML and 4.8 months in Ph(+) ALL. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention.
  
  
  CONCLUSIONS
  This report describes the Food and Drug Administration review supporting the approval of dasatinib for CML and Ph(+) ALL based on the rates and durability of cytogenetic and hematologic responses.
authors.affiliation: Office of Oncology Drug Products, Office of New Drugs, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA. michael.brave@fda.hhs.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Brave
authors.forename: Vicki
authors.initials: V
authors.lastname: Goodman
authors.forename: Edvardas
authors.initials: E
authors.lastname: Kaminskas
authors.forename: Ann
authors.initials: A
authors.lastname: Farrell
authors.forename: William
authors.initials: W
authors.lastname: Timmer
authors.forename: Sarah
authors.initials: S
authors.lastname: Pope
authors.forename: Ravi
authors.initials: R
authors.lastname: Harapanhalli
authors.forename: Haleh
authors.initials: H
authors.lastname: Saber
authors.forename: David
authors.initials: D
authors.lastname: Morse
authors.forename: Julie
authors.initials: J
authors.lastname: Bullock
authors.forename: Angela
authors.initials: A
authors.lastname: Men
authors.forename: Carol
authors.initials: C
authors.lastname: Noory
authors.forename: Roshni
authors.initials: R
authors.lastname: Ramchandani
authors.forename: Leslie
authors.initials: L
authors.lastname: Kenna
authors.forename: Brian
authors.initials: B
authors.lastname: Booth
authors.forename: Joga
authors.initials: J
authors.lastname: Gobburu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000069439:Dasatinib; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib