Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the

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Cancer. 2007 Oct 1;110(7):1542-50.
Phase
2 study of temozolomide in children and adolescents with recurrent
central nervous system tumors: a report from the Children's Oncology
Group.
Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH.
Department of Pediatrics, Oregon Health Science & University, Portland, Oregon, USA.


BACKGROUND:
Effective chemotherapy is lacking for most types of central nervous
system (CNS) tumors in children. Temozolomide, an agent with activity
against adult brain tumors, was investigated in children and
adolescents with recurrent CNS tumors. METHODS: Temozolomide was
administered orally as monthly 5-day courses at doses of 200 mg/m(2)/d
(patients with no prior craniospinal irradiation [CSI]) or 180
mg/m(2)/d (prior CSI). Patients with a complete (CR) or partial (PR)
response or stable disease (SD) could continue temozolomide for up to
12 cycles.
RESULTS: The cohort comprised 122 patients, including 113
with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104
evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs
occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1
of 21 with low-grade astrocytoma, and 3 of 25 with
medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred
in an additional patient with medulloblastoma/PNET. No responses were
observed in patients with ependymoma, brain-stem glioma, or other CNS
tumors. Notably, 41% of patients with low-grade astrocytoma had SD
through 12 courses. The most frequent toxicities were grade 3 or 4
neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity
was infrequent.
CONCLUSIONS: Although overall objective responses were
limited, further exploration of temozolomide may be warranted in
children with medulloblastoma and other PNETs, or in patients with
low-grade astrocytoma, perhaps in a setting of less pretreatment than
the patients in the current study, or in the context of multiagent
therapy.