Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Birgit Geoerger, Mark W. Kieran, Stephan Grupp, Danuta Perek, Jill Clancy, ...
PurposeA phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Patients and methodsTemsirolimus 75 mg/mwas 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).ResultsFifty-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.ConclusionsTemsirolimus administered weekly at the dose of 75 mg/mdid 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.
Júlio Leonardo B. Pereira
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