UNLABELLED: 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-β 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/m²/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/m² dose levels. At 110 mg/m², two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m²), grade 3 diarrhea (85 mg/m²), and grade 2 creatinine elevation (50 mg/m²) 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.
UNLABELLED: 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-β 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/m²/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/m² dose levels. At 110 mg/m², two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m²), grade 3 diarrhea (85 mg/m²), and grade 2 creatinine elevation (50 mg/m²) 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.
Authors: Hagop Kantarjian; Susan O'Brien; Jorge Cortes; William Wierda; Stefan Faderl; Guillermo Garcia-Manero; Jean-Pierre Issa; Elihu Estey; Michael Keating; Emil J Freireich Journal: Cancer Date: 2008-10-01 Impact factor: 6.860
Authors: Moshe Talpaz; Neil P Shah; Hagop Kantarjian; Nicholas Donato; John Nicoll; Ron Paquette; Jorge Cortes; Susan O'Brien; Claude Nicaise; Eric Bleickardt; M Anne Blackwood-Chirchir; Vishwanath Iyer; Tai-Tsang Chen; Fei Huang; Arthur P Decillis; Charles L Sawyers Journal: N Engl J Med Date: 2006-06-15 Impact factor: 91.245
Authors: Jorge Cortes; Philippe Rousselot; Dong-Wook Kim; Ellen Ritchie; Nelson Hamerschlak; Steven Coutre; Andreas Hochhaus; Francois Guilhot; Giuseppe Saglio; Jane Apperley; Oliver Ottmann; Neil Shah; Philipp Erben; Susan Branford; Prasheen Agarwal; Ashwin Gollerkeri; Michele Baccarani Journal: Blood Date: 2006-12-21 Impact factor: 22.113
Authors: Andreas Hochhaus; Hagop M Kantarjian; Michele Baccarani; Jeffrey H Lipton; Jane F Apperley; Brian J Druker; Thierry Facon; Stuart L Goldberg; Francisco Cervantes; Dietger Niederwieser; Richard T Silver; Richard M Stone; Timothy P Hughes; Martin C Muller; Rana Ezzeddine; Athena M Countouriotis; Neil P Shah Journal: Blood Date: 2006-11-30 Impact factor: 22.113
Authors: Oliver Ottmann; Hervé Dombret; Giovanni Martinelli; Bengt Simonsson; Francois Guilhot; Richard A Larson; Giovanna Rege-Cambrin; Jerald Radich; Andreas Hochhaus; Anne Marie Apanovitch; Ashwin Gollerkeri; Steven Coutre Journal: Blood Date: 2007-05-11 Impact factor: 22.113
Authors: George D Demetri; Patricia Lo Russo; Iain R J MacPherson; Ding Wang; Jeffrey A Morgan; Valerie G Brunton; Prashni Paliwal; Shruti Agrawal; Maurizio Voi; T R Jeffry Evans Journal: Clin Cancer Res Date: 2009-09-29 Impact factor: 12.531
Authors: Lisa J Christopher; Donghui Cui; Chiyuan Wu; Roger Luo; James A Manning; Samuel J Bonacorsi; Michael Lago; Alban Allentoff; Francis Y F Lee; Betty McCann; Susan Galbraith; Donald P Reitberg; Kan He; Anthony Barros; Anne Blackwood-Chirchir; W Griffith Humphreys; Ramaswamy A Iyer Journal: Drug Metab Dispos Date: 2008-04-17 Impact factor: 3.922
Authors: E Anders Kolb; Richard Gorlick; Peter J Houghton; Christopher L Morton; Richard B Lock; Mayamin Tajbakhsh; C Patrick Reynolds; John M Maris; Stephen T Keir; Catherine A Billups; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2008-06 Impact factor: 3.167
Authors: Viswanath Reddy Belum; Courtney Washington; Christine A Pratilas; Vincent Sibaud; Franck Boralevi; Mario E Lacouture Journal: Pediatr Blood Cancer Date: 2015-02-12 Impact factor: 3.167
Authors: Nathan J Robison; Kee Kiat Yeo; Adrian P Berliner; Jemily Malvar; Michael A Sheard; Ashley S Margol; Robert C Seeger; Teresa Rushing; Jonathan L Finlay; Richard Sposto; Girish Dhall Journal: J Neurooncol Date: 2018-02-09 Impact factor: 4.130
Authors: Alberto Broniscer; Sujuan Jia; Belinda Mandrell; Dima Hamideh; Jie Huang; Arzu Onar-Thomas; Amar Gajjar; Susana C Raimondi; Ruth G Tatevossian; Clinton F Stewart Journal: Pediatr Blood Cancer Date: 2018-03-07 Impact factor: 3.167