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Medline ® Abstract for Reference 94

of 'Treatment of relapsed or refractory chronic lymphocytic leukemia'

Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia.
Amrein PC, Attar EC, Takvorian T, Hochberg EP, Ballen KK, Leahy KM, Fisher DC, Lacasce AS, Jacobsen ED, Armand P, Hasserjian RP, Werner L, Neuberg D, Brown JR
Clin Cancer Res. 2011;17(9):2977. Epub 2011 Mar 14.
PURPOSE: 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.
EXPERIMENTAL DESIGN: 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 responsesby 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.
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.