Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.

2.50
Hdl Handle:
http://hdl.handle.net/10541/80237
Title:
Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.
Authors:
Lashford, Linda S; Thiesse, P; Jouvet, A; Jaspan, T; Couanet, D; Griffiths, P D; Doz, F; Ironside, Janet A D; Robson, K; Hobson, R; Dugan, M; Pearson, A D J; Vassal, G; Frappaz, D
Abstract:
PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.
Affiliation:
Christie National Health Service Trust, Manchester. llashford@crc.org.uk
Citation:
Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. 2002, 20 (24):4684-91 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
15-Dec-2002
URI:
http://hdl.handle.net/10541/80237
DOI:
10.1200/JCO.2002.08.141
PubMed ID:
12488414
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLashford, Linda S-
dc.contributor.authorThiesse, P-
dc.contributor.authorJouvet, A-
dc.contributor.authorJaspan, T-
dc.contributor.authorCouanet, D-
dc.contributor.authorGriffiths, P D-
dc.contributor.authorDoz, F-
dc.contributor.authorIronside, Janet A D-
dc.contributor.authorRobson, K-
dc.contributor.authorHobson, R-
dc.contributor.authorDugan, M-
dc.contributor.authorPearson, A D J-
dc.contributor.authorVassal, G-
dc.contributor.authorFrappaz, D-
dc.date.accessioned2009-09-08T10:18:45Z-
dc.date.available2009-09-08T10:18:45Z-
dc.date.issued2002-12-15-
dc.identifier.citationTemozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. 2002, 20 (24):4684-91 J. Clin. Oncol.en
dc.identifier.issn0732-183X-
dc.identifier.pmid12488414-
dc.identifier.doi10.1200/JCO.2002.08.141-
dc.identifier.urihttp://hdl.handle.net/10541/80237-
dc.description.abstractPURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.en
dc.language.isoenen
dc.subjectBrain Canceren
dc.subject.meshAdolescent-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBone Marrow-
dc.subject.meshBrain Neoplasms-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshDacarbazine-
dc.subject.meshFemale-
dc.subject.meshGlioma-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshThrombocytopenia-
dc.titleTemozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.en
dc.typeArticleen
dc.contributor.departmentChristie National Health Service Trust, Manchester. llashford@crc.org.uken
dc.identifier.journalJournal of Clinical Oncologyen

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