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Updated: Jul 17, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children's Oncology
Mason Bond1, Mark L Bernstein, Alberto Pappo
1B.C. Children's Hospital, Vancouver, British Columbia, Canada. mbond@cw.bc.ca
Background:
Imatinib mesylate is a small molecule inhibitor of certain tyrosine kinases, most notably the chimeric bcr-abl fusion protein found in CML. It also inhibits KIT and PDGF receptor tyrosine kinases in vitro. Ewing sarcoma, osteosarcoma, neuroblastoma, desmoplastic small round cell, and synovial sarcomas often overexpress KIT or the PDGF receptor. A phase II study of imatinib in children and young adults with select solid tumors was performed.
Procedure:
Patients less than 30 years of age with refractory or recurrent Ewing sarcoma, osteosarcoma, neuroblastoma, desmoplastic small round cell, synovial sarcomas or GIST were eligible. Imatinib was administered daily for 28 day courses at a dose of 440 mg/m(2)/day. Responses were assessed according to Response Evaluation Criteria in Solid Tumor (RECIST).
Results:
Seventy eligible patients, 48 male and 22 female, were enrolled and 59 were evaluable for response. Only one partial response was seen among 24 patients with Ewing sarcoma. There were no other objective responses. Hemorrhagic pleural effusions occurred in seven patients with pulmonary lesions, four of whom had progressive disease at the time of the hemorrhage. Intratumoral bleeding was reported in three additional patients.
Conclusion:
Imatinib as a single agent at a dose of 440 mg/m(2)/day demonstrated little or no activity as a single agent in children with relapsed or refractory Ewing sarcoma, osteosarcoma, neuroblastoma, or desmoplastic small round cell tumors.
Insights
This study found imatinib showed minimal effectiveness in treating pediatric solid tumors like Ewing sarcoma. Further research is needed for these rare cancers.
Area of Science:
- Oncology
- Pharmacology
Background:
- Imatinib mesylate targets tyrosine kinases, including KIT and PDGF receptors, often overexpressed in pediatric solid tumors.
- These include Ewing sarcoma, osteosarcoma, neuroblastoma, and synovial sarcomas.
Purpose of the Study:
- To evaluate the efficacy of imatinib in children and young adults with refractory or recurrent select solid tumors.
- To assess response rates and toxicity of imatinib in this patient population.
Main Methods:
- A Phase II study enrolled patients under 30 with specific refractory/recurrent solid tumors.
- Imatinib was administered at 440 mg/m(2)/day for 28-day cycles.
- Tumor response was evaluated using RECIST criteria.
Main Results:
- Fifty-nine patients were evaluable for response; only one partial response was observed in 24 Ewing sarcoma patients.
- No other objective responses were noted across the studied tumor types.
- Adverse events included hemorrhagic pleural effusions and intratumoral bleeding.
Conclusions:
- Imatinib monotherapy demonstrated limited activity in pediatric patients with relapsed or refractory Ewing sarcoma, osteosarcoma, neuroblastoma, and desmoplastic small round cell tumors.
- The observed toxicity warrants careful consideration in this patient group.
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