Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma

Eur J Cancer. 2012 Jan;48(2):253-62. doi: 10.1016/j.ejca.2011.09.021. Epub 2011 Oct 25.


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.

Trial registration: NCT00106353.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / 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*
  • Sirolimus / pharmacokinetics
  • Sirolimus / therapeutic use


  • Antineoplastic Agents
  • temsirolimus
  • Sirolimus

Associated data