TY - JOUR
T1 - Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia
T2 - Results from a Children's Oncology Group phase 1 study
AU - Champagne, Martin A.
AU - Capdeville, Renaud
AU - Krailo, Mark
AU - Qu, Wenchun
AU - Peng, Bin
AU - Rosamilia, Marianne
AU - Therrien, Martine
AU - Zoellner, Ulrike
AU - Blaney, Susan M.
AU - Bernstein, Mark
PY - 2004/11/1
Y1 - 2004/11/1
N2 - The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph+) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m2. Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m2 dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m2. Doses of 260 and 340 mg/m2 provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.
AB - The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph+) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m2. Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m2 dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m2. Doses of 260 and 340 mg/m2 provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.
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U2 - 10.1182/blood-2003-09-3032
DO - 10.1182/blood-2003-09-3032
M3 - Article
C2 - 15231574
AN - SCOPUS:20844452050
SN - 0006-4971
VL - 104
SP - 2655
EP - 2660
JO - Blood
JF - Blood
IS - 9
ER -