1. ¹III Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany
2. ²Department of Hematology–Oncology 'L and A Seràgnoli,' S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
3. ³OHSU Cancer Institute, Oregon Health & Science University, Portland, OR, USA
4. ⁴Department of Haematology, Hammersmith Hospital, Imperial College, London, UK
5. ⁵Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada
6. ⁶The Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA
7. ⁷Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France
8. ⁸Division of Hematology/Oncology, San Francisco School of Medicine, University of California, San Francisco, CA, USA
9. ⁹Department of Hematology, Hospital Clinic i Provincial, Barcelona, Spain
10. ¹⁰Division of Hematology/Oncology, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY, USA
11. ¹¹Department of Hematology, Oncology and Coagulation, University of Leipzig, Leipzig, Germany
12. ¹²Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
13. ¹³Service Clinique des Maladies du Sang, Hôpital Saint-Louis, Paris, France
14. ¹⁴Department of Medicine, University of Chicago, Chicago, IL, USA
15. ¹⁵Clinical Research Center, CHU de Poitiers, Poitiers, France
16. ¹⁶Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia
17. ¹⁷Bristol–Myers Squibb, Wallingford, CT, USA
18. ¹⁸Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Professor Dr A Hochhaus, Abteilung fuer Leukaemieforschung, III Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Wiesbadener Strasse 7-11, 68167 Mannheim, Germany. E-mail: hochhaus@uni-hd.de

Received 27 February 2008; Accepted 7 March 2008; Published online 10 April 2008.

Abstract

Dasatinib, a potent inhibitor of BCR–ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1–18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96% . Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37% ), headache (32% ), fatigue (31% ), dyspnea (30% ) and pleural effusion (27% ). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.