TY - JOUR
T1 - EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma
AU - Franceschi, Enrico
AU - Stupp, Roger
AU - Van Den Bent, Martin J.
AU - Van Herpen, Carla
AU - Laigle Donadey, Florence
AU - Gorlia, Thierry
AU - Hegi, Monika
AU - Lhermitte, Benoit
AU - Strauss, Lewis C.
AU - Allgeier, Anouk
AU - Lacombe, Denis
AU - Brandes, Alba A.
PY - 2012/12
Y1 - 2012/12
N2 - 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/m2) 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.
AB - 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/m2) 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.
KW - CCNU
KW - dasatinib
KW - recurrent glioblastoma
UR - http://www.scopus.com/inward/record.url?scp=84869189499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869189499&partnerID=8YFLogxK
U2 - 10.1093/neuonc/nos256
DO - 10.1093/neuonc/nos256
M3 - Article
C2 - 23090987
AN - SCOPUS:84869189499
SN - 1522-8517
VL - 14
SP - 1503
EP - 1510
JO - Neuro-oncology
JF - Neuro-oncology
IS - 12
ER -
