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

被引:105
|
作者
Geoerger, Birgit [1 ]
Kieran, Mark W. [2 ,3 ]
Grupp, Stephan [4 ]
Perek, Danuta [5 ]
Clancy, Jill [6 ]
Krygowski, Mizue [7 ]
Ananthakrishnan, Revathi [6 ]
Boni, Joseph P. [8 ]
Berkenblit, Anna [8 ]
Spunt, Sheri L. [9 ,10 ]
机构
[1] Univ Paris 11, Inst Gustave Roussy, Dept Paediat & Adolescent Med, F-94805 Villejuif, France
[2] Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Childrens Hosp, Boston, MA 02115 USA
[4] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[5] Childrens Mem Hlth Inst, Warsaw, Poland
[6] inVentiv Clin Solut, Cambridge, MA USA
[7] Pfizer Oncol Res, Cambridge, MA USA
[8] Pfizer Oncol Res, Collegeville, PA USA
[9] St Jude Childrens Res Hosp, Memphis, TN 38105 USA
[10] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
关键词
Temsirolimus; mTOR; Child; Adolescent; Glioma; Neuroblastoma; Rhabdomyosarcoma; Clinical trial; Phase II; MAMMALIAN TARGET; CHILDHOOD-CANCER; MTOR INHIBITION; CCI-779; PATHWAY; GROWTH; COMBINATION; SURVIVORS; EVALUATE;
D O I
10.1016/j.ejca.2011.09.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:253 / 262
页数:10
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