Publication Date:
2005-11-16
Description:
Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases. Data from a phase I study suggest that dasatinib exhibits potent activity with high hematologic and cytogenetic response rates in CML patients with myeloid blast crisis (MBC) who were imatinib (IM)-resistant (IM-R) or -intolerant (IM-I). Here we report the preliminary results from one Phase II trial (Study CA180006 or ‘START-B’) in MBC, which was initiated in December 2004. This open-label study was carried out in 37 centers worldwide between December 2004 and May 2005. A total of 74 IM-R or IM-I MBC pts were accrued (41 male, median age 56 years [range 21–71]). Preliminary data are currently available on the first 34 pts (29 IM-R and 5 IM-I). Dasatinib was administered orally, at a dose of 70 mg twice daily (BID) in a continuous daily dosing schedule; dose escalation to 100 mg BID was permitted for patients who did not achieve hematologic response and dose reduction to 50 mg and 40 mg BID was allowed in the presence of persistent toxicity. Complete blood counts were performed weekly and bone marrow assessment, including cytogenetic analysis, was performed monthly. Mutations in the BCR-ABL domain were assessed in all pts. Pretreatment characteristics of these 34 pts included: 71% male, median age 54 years (range 21 – 71). Median duration of CML from first diagnosis was 49.3 months (range 5.6 – 215.5). Prior therapy included bone marrow transplant (5 pts, 15%) and interferon (18 pts, 53%). In 44% of pts, the highest IM dose was 〉600 mg/day and 41% of pts received IM for 〉3 years. Best responses to IM were complete hematologic response (CHR) in 82% of pts and major cytogenetic response in 39% of pts (complete in 27%, and partial in 12%). At baseline, 35% of pts had a WBC count ≥20 x 103/mm3, 71% had a platelet count
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink
