科研之友
微信
新浪微博
Facebook
分享链接
摘要
Purpose Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-beta receptor. Dasatinib was found to have selective activity in several tumor models in the Pediatric Preclinical Testing Program. Patients and Methods A phase I study of dasatinib in pediatric patients with refractory solid tumors or imatinib-refractory, Philadelphia chromosome-positive leukemia was performed. Dose levels of 50, 65, 85, and 110 mg/m(2)/dose, administered orally twice daily for 28 days, with courses repeated without interruption, were studied. Pharmacokinetic studies were performed with the initial dose. Results A total of 39 patients (solid tumors, n = 28; chronic myeloid leukemia [CML], n = 9; acute lymphoblastic leukemia, n = 2) were enrolled. No dose-limiting toxicities (DLTs) were observed at the 50, 65, and 85 mg/m(2) dose levels. At 110 mg/m(2), two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m(2)), grade 3 diarrhea (85 mg/m(2)), and grade 2 creatinine elevation (50 mg/m(2)) were observed. DLT in later courses included pleural effusions, hemangiomatosis, and GI hemorrhage. There were three complete cytogenetic responses, three partial cytogenetic responses, and two partial/minimal cytogenetic responses observed in evaluable patients with CML. Conclusion Overall, drug disposition and tolerability of dasatinib were similar to those observed in adult patients. J Clin Oncol 29:839-844.
- 出版日期2011-3-1
