Details

Autor(en) / Beteiligte

• Franceschi, Enrico
• Stupp, Roger
• van den Bent, Martin J
• van Herpen, Carla
• Laigle Donadey, Florence
• Gorlia, Thierry
• Hegi, Monika
• Lhermitte, Benoit
• Strauss, Lewis C
• Allgeier, Anouk
• Lacombe, Denis
• Brandes, Alba A

Titel

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2012-12, Vol.14 (12), p.1503-1510

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7-9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90-110 mg/m(2)) and dasatinib (100-200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.