Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours.
Details
Serval ID
serval:BIB_681D296F19E6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours.
Journal
European journal of cancer
ISSN
0959-8049 (Print)
ISSN-L
0959-8049
Publication state
Published
Issued date
09/2006
Peer-reviewed
Oui
Volume
42
Number
14
Pages
2335-2342
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The aims of this study were to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetics of oral temozolomide administered over 42 d in children with recurrent/refractory brain tumours. Cohorts of 3-6 patients were treated for 42 d, followed by a 7-d rest period for a maximum of 6 cycles. Patients were stratified as heavily pre-treated (HPT) and non-heavily pre-treated (NHPT). Starting doses were 50 mg/m2 (HPT) or 75 mg/m2 (NHPT). Out of 28 patients enrolled, 20 were evaluable for toxicity and 19 for pharmacokinetics. Three patients in the NHPT group developed grade 3/4 haematological toxicity, 2 experienced dose-limiting toxicity (thrombocytopenia) at 100 mg/m2, and 9/20 developed grade 3 lymphopenia. MTD in both strata was 85 mg/m2. Responses were observed in 4 patients: 2 complete responses (CR) in medulloblastoma and supratentorial primitive neuroectodermal tumours (PNET), and 2 partial responses (PR) in high-grade glioma, respectively. Overall cumulative exposure was at least 1.5 times higher than in the 5-d administration schedule. In conclusion, the recommended dose of temozolomide is 85 mg/m2 x 42 d. Dose-limiting toxicities are thrombocytopenia and lymphopenia. The observed response rate warrants phase II studies.
Keywords
Administration, Oral, Antineoplastic Agents, Alkylating/administration & dosage, Antineoplastic Agents, Alkylating/adverse effects, Antineoplastic Agents, Alkylating/pharmacokinetics, Brain Neoplasms/drug therapy, Brain Neoplasms/pathology, Child, Dacarbazine/administration & dosage, Dacarbazine/adverse effects, Dacarbazine/analogs & derivatives, Dacarbazine/pharmacokinetics, Dose-Response Relationship, Drug, Drug Administration Schedule, Feasibility Studies, Female, Humans, Male, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/pathology, Temozolomide
Pubmed
Web of science
Create date
10/01/2019 18:52
Last modification date
20/08/2019 15:23