Originally published as JCO Early Release 10.1200/JCO.2007.14.3339 on June 1 2009

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Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial

From the Hammersmith Hospital, Imperial College, London, United Kingdom; The University of Texas M. D. Anderson Cancer Center, Houston, TX; St Mary's Hospital, the Catholic University of Korea, Seoul; Chonnam National University, Hwasun-gun, Jeollanam-do, Korea; Clinical Research Center, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY; S Orsola-Malpighi University Hospital, Bologna; Ospedale S. Eugenio, Rome, Italy; British Hospital of Buenos Aires, Argentina; Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany; University Hospital, Basel, Switzerland; Universidade Estadual De Campinas, Campinas, Brazil; University of Chicago, Chicago, IL; Princess Margaret Hospital, Toronto, Ontario, Canada; Emory University School of Medicine, Atlanta, GA; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; University of Adelaide, Adelaide, Australia; Bristol-Myers Squibb, Wallingford, CT; and Dana-Farber Cancer Institute, Boston, MA.

Corresponding author: Jane F. Apperley, MD, Hammersmith Hospital, Imperial College School of Medicine, Du Cane Rd, London W12 0NN, United Kingdom; e-mail: j.apperley{at}imperial.ac.uk.

Purpose Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population.

Patients and Methods Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily.

Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%).

Conclusion Dasatinib is effective in patients with CML-AP after imatinib treatment failure.

Supported by Bristol-Myers Squibb.

This trial is registered at www.clinicaltrials.gov (Trial No. CA180-005).

Presented in part at the American Society of Hematology Annual Meeting, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00101647.

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