A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a Children's Oncology Group study.
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.


METHODS
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.


CONCLUSIONS
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.
Bond
Mason
M
B.C. Children's Hospital, Vancouver, British Columbia, Canada. mbond@cw.bc.ca
Bernstein
Mark L
ML
Pappo
Alberto
A
Schultz
Kirk R
KR
Krailo
Mark
M
Blaney
Susan M
SM
Adamson
Peter C
PC
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012512:Sarcoma, Ewing / Q000188:drug therapy; D013584:Sarcoma, Synovial / Q000188:drug therapy
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate