PURPOSE: A phase II study of temsirolimus was conducted in children and 
adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.
PATIENTS AND METHODS: Temsirolimus 75 mg/m(2) was administered once weekly until 
disease progression or intolerance. Using the Simon 2-stage design, further 
enrolment in each disease cohort required ≥ 2 objective responses within the 
first 12 weeks for the first 12 evaluable patients (those who received ≥ 3 
temsirolimus doses).
RESULTS: Fifty-two heavily pretreated patients with relapsed (12%) or refractory 
(88%) disease, median age 8 years (range 1-21 years), were enroled and treated. 
One patient with neuroblastoma achieved confirmed partial response within the 
first 12 weeks; thus, none of the 3 cohorts met the criterion for continued 
enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients 
(41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma 
multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 
of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the 
three cohorts, median duration of stable disease or better was 128, 663 and 75 
d, respectively. The most common treatment-related adverse events were 
thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were 
similar to those observed in adults.
CONCLUSIONS: Temsirolimus administered weekly at the dose of 75 mg/m(2) did not 
meet the primary objective efficacy threshold in children with high-grade 
glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable 
disease merits further evaluation in combination therapy.