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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
Lashford
LS, Thiesse P, Jouvet A, Jaspan T, Couanet D, Griffiths PD, Doz F, Ironside J,
Robson K, Hobson R, Dugan M, Pearson AD, Vassal G, Frappaz D
Christie
National Health Service Trust, Manchester
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.
PMID:
12488414 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12488414&dopt=Abstract
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