EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma.

Details

Serval ID
serval:BIB_3986E4D28864
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma.
Journal
European Journal of Cancer
Author(s)
Brandes A.A., Stupp R., Hau P., Lacombe D., Gorlia T., Tosoni A., Mirimanoff R.O., Kros J.M., van den Bent M.J.
ISSN
1879-0852[electronic], 0959-8049[linking]
Publication state
Published
Issued date
2010
Volume
46
Number
2
Pages
348-354
Language
english
Abstract
BACKGROUND: Glioblastoma is a highly vascularised tumour with a high expression of both vascular endothelial growth factor (VEGF) and VEGFR. PTK787/ZK222584 (PTK/ZK, vatalanib), a multiple VEGF receptor inhibitor, blocks the intracellular tyrosine kinase activity of all known VEGF receptors and is therefore suitable for long-term therapy of pathologic tumour neovascularisation.
PATIENTS AND METHODS: The study was designed as an open-label, phase I/II study. A classic 3+3 design was selected. PTK/ZK was added to standard concomitant and adjuvant treatment, beginning in the morning of day 1 of radiotherapy (RT), and given continuously until disease progression or toxicity. PTK/ZK doses started from 500 mg with subsequent escalations to 1000 and 1250 mg/d. Adjuvant or maintenance PTK after the end of radiochemotherapy was given at a previously established dose of 750 mg twice daily continuously with TMZ at the standard adjuvant dose. RESULTS: Twenty patients were enrolled. Dose-limiting toxicities at a once daily dose of 1250 mg were grade 3 diarrhoea (n=1), grade 3 ALT increase (n=2), and myelosuppression with grade 4 thrombocytopenia and neutropenia (n=1). The recommended dose of PTK/ZK in combination with radiotherapy and temozolomide (TMZ) is 1000 mg once a day. This treatment is safe and well tolerated.
CONCLUSION: In our phase I study once daily administration of up to 1000 mg of PTK/ZK in conjunction with concomitant temozolomide and radiotherapy was feasible and safe. Prolonged administration of this oral agent is manageable. The planned randomised phase II trial was discontinued right at its onset due to industry decision not to further develop this agent.
Keywords
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Brain Neoplasms/drug therapy, Brain Neoplasms/radiotherapy, Chemotherapy, Adjuvant, Dacarbazine/administration & dosage, Dacarbazine/adverse effects, Female, Glioblastoma/drug therapy, Glioblastoma/radiotherapy, Humans, Male, Maximum Tolerated Dose, Middle Aged, Phthalazines/administration & dosage, Phthalazines/adverse effects, Pyridines/administration & dosage, Pyridines/adverse effects, Radiotherapy, Adjuvant, Treatment Outcome
Pubmed
Web of science
Create date
08/01/2010 15:07
Last modification date
20/08/2019 13:29
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