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
Title
Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours.
Journal
European journal of cancer
Author(s)
Baruchel S., Diezi M., Hargrave D., Stempak D., Gammon J., Moghrabi A., Coppes M.J., Fernandez C.V., Bouffet E.
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
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 17:52
Last modification date
20/08/2019 14:23
Usage data