Back to Search
Start Over
Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors.
- Source :
-
Neuro-oncology [Neuro Oncol] 2011 Jan; Vol. 13 (1), pp. 109-18. Date of Electronic Publication: 2010 Oct 25. - Publication Year :
- 2011
-
Abstract
- This multicenter phase I study aimed to establish the recommended dose (RD) of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, given as monotherapy or with radiotherapy to children with malignant brain tumors. Group 1 included patients with refractory or relapsing brain tumors receiving erlotinib alone, and group 2 included newly diagnosed patients with brainstem gliomas receiving radiotherapy and erlotinib. A conventional 3 + 3 dose escalation and a continual reassessment method, respectively, were utilized in 4 dose levels: 75, 100, 125, and 150 mg/m² per day. Fifty-one children were enrolled (30 and 21, respectively); 50 received treatment. The RD of erlotinib was 125 mg/m² per day as monotherapy or in combination with radiotherapy. Overall, 230 adverse events in 44 patients were possibly treatment related (216, grades 1 and 2; 9, grade 3; 1, grade 4; 4, grade 5). Dermatologic and neurologic symptoms were common; intratumoral hemorrhage was confirmed in 3 patients. In group 1, 8 of 29 patients (28%) had stable disease with tumor regression approaching 50% in a malignant glioma and an anaplastic oligoastrocytoma. In group 2, overall survival was 12.0 months. EGFR overexpression by immunohistochemistry was found in 17 of 38 (45%) tumor samples analyzed, with a partial gain of 7p11.2 in 1 glioblastoma; phosphate and tensin homolog loss was frequent in brainstem glioma (15 of 19). Mean (95% CI) apparent clearance and volume of distribution for erlotinib were 4.0 L/h (3.4-4.5 L/h) and 98.6 L (69.8-127.0 L), respectively, and were independent of the dose level; mean half-life was 16.6 hours. Thus, erlotinib 125 mg/m² per day has an acceptable tolerability profile in pediatric patients with brain tumors and can be combined with radiotherapy.
- Subjects :
- Adolescent
Adult
Child
Child, Preschool
Erlotinib Hydrochloride
Female
Humans
Infant
Male
Maximum Tolerated Dose
Protein Kinase Inhibitors pharmacokinetics
Quinazolines pharmacokinetics
Survival Rate
Therapies, Investigational
Tissue Distribution
Treatment Outcome
Young Adult
Brain Stem Neoplasms drug therapy
Glioma drug therapy
Neoplasm Recurrence, Local drug therapy
Protein Kinase Inhibitors therapeutic use
Quinazolines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5866
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20974795
- Full Text :
- https://doi.org/10.1093/neuonc/noq141