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.