Abstract | PURPOSE: 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.
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Authors | Birgit Geoerger, Mark W Kieran, Stephan Grupp, Danuta Perek, Jill Clancy, Mizue Krygowski, Revathi Ananthakrishnan, Joseph P Boni, Anna Berkenblit, Sheri L Spunt |
Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 48
Issue 2
Pg. 253-62
(Jan 2012)
ISSN: 1879-0852 [Electronic] England |
PMID | 22033322
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- temsirolimus
- Sirolimus
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Topics |
- Adolescent
- Adult
- Antineoplastic Agents
(pharmacokinetics, therapeutic use)
- Brain Neoplasms
(drug therapy)
- Child
- Child, Preschool
- Cohort Studies
- Disease Progression
- Female
- Glioma
(drug therapy)
- Humans
- Infusions, Intravenous
- Male
- Neuroblastoma
(drug therapy)
- Rhabdomyosarcoma
(drug therapy)
- Sirolimus
(analogs & derivatives, pharmacokinetics, therapeutic use)
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