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

Lookup NU author(s): Dr Paul Griffiths, Professor Andrew Pearson

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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.


Publication metadata

Author(s): Lashford LS, Thiesse P, Jouvet A, Jaspan T, Couanet D, Griffiths PD, Doz F, Ironside J, Robson K, Hobson R, Dugan M, Pearson ADJ, Vassal G, Frappaz D

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Oncology

Year: 2002

Volume: 20

Issue: 24

Pages: 4684-4691

ISSN (print): 0732-183X

ISSN (electronic): 1527-7755

URL: http://dx.doi.org/10.1200/JCO.2002.08.141

DOI: 10.1200/JCO.2002.08.141

PubMed id: 12488414


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