Journal of Clinical Oncology, Vol 20, Issue 24
(December), 2002: 4684-4691
© 2002 American Society for Clinical Oncology
Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study
By L. S. Lashford,
P. Thiesse,
A. Jouvet,
T. Jaspan,
D. Couanet,
P. D. Griffiths,
F. Doz,
J. Ironside,
K. Robson,
R. Hobson,
M. Dugan,
A. D.J. Pearson,
G. Vassal,
D. Frappaz
From Christie National Health Service Trust, Manchester; Queens Medical Centre, Nottingham; Royal Hallamshire Hospital, Sheffield; Western General Hospital, Edinburgh; United Kingdom Children’s Cancer Study Group Data Centre, Leicester; and Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; Centre Leon Berard and Hopital Neurologique, Lyon; Institut Gustav Roussy, Villejuif; and Institut Curie, Paris, France; and Schering-Plough, Kenilworth, NJ.
Address reprint requests to L.S. Lashford, MD, Translational Research and Experimental Therapeutics, The Cancer Research Campaign, 10 Cambridge Terr, London NW1 4JL, United Kingdom; email: llashford{at}crc.org.uk
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/m2 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.
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