Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours
| Autor: | Sylvain Baruchel, Janet Gammon, Darren Hargrave, Albert Moghrabi, M. Diezi, Max J. Coppes, Eric Bouffet, Conrad V. Fernandez, Diana Stempak |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Dacarbazine Administration Oral Drug Administration Schedule Pharmacokinetics Refractory Internal medicine Glioma Temozolomide medicine Humans Child Antineoplastic Agents Alkylating Medulloblastoma Dose-Response Relationship Drug Brain Neoplasms business.industry medicine.disease Dose–response relationship Anesthesia Toxicity Feasibility Studies Female Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | European Journal of Cancer. 42:2335-2342 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2006.03.023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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