title: Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we tested the activity of dasatinib in patients with relapsed CLL.
  
  
  METHODS
  Patients were eligible for this phase II trial if they had documented CLL/SLL and had failed at least 1 prior therapy with a fludarabine-containing regimen and if they required therapy according to NCI-WG criteria. The starting dose of dasatinib was 140 mg daily.
  
  
  RESULTS
  Fifteen patients were enrolled, with a median age of 59 and a median of 3 prior regimens. All patients had received fludarabine, and 5 were fludarabine-refractory. Eleven of the 15 (73%) had high risk del(11q) or del(17p) cytogenetics. The primary toxicity was myelosuppression, with grade 3 or 4 neutropenia and thrombocytopenia in 10 and 6 patients, respectively. Partial responses by NCI-WG criteria were achieved in 3 of the 15 patients (20%; 90% CI: 6-44). Among the remaining 12 patients, 5 had nodal responses by physical exam, and 1 patient had a nodal and lymphocyte response but with severe myelosuppression. Pharmacodynamic studies indicated apoptosis in peripheral blood CLL cells within 3 to 6 hours after dasatinib administration, associated with downregulation of Syk (spleen tyrosine kinase) mRNA.
  
  
  CONCLUSIONS
  Dasatinib as a single agent has activity in relapsed and refractory CLL.
authors.affiliation: Massachusetts General Hospital Cancer Center, Medical Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Amrein
authors.forename: Eyal C
authors.initials: EC
authors.lastname: Attar
authors.forename: Tak
authors.initials: T
authors.lastname: Takvorian
authors.forename: Ephraim P
authors.initials: EP
authors.lastname: Hochberg
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Leahy
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Ann S
authors.initials: AS
authors.lastname: Lacasce
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jacobsen
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011860:Radiography, Abdominal; D012008:Recurrence; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib