gms | German Medical Science

Introduction: GBM is a platelet derived growth factor receptor (PDGF-R) positive malignant brain tumor with a median survival of less than 15 months. While single agent Imatinib (I) did not show significant activity the combination of I plus Hydroxyurea (HU) could demonstrate efficacy in a group of 30 progressive pretreated GBM patients with progression free survival at 6 months and 24 months of and 16 % respectively. 37 % of the patients eperienced a stable disease (SD) as best response with longterm stabilisation for more than 2 years being possible. GBM although one of the most aggressive solid tumors usually shows a short period of disease stabilisation after primary treatment or effective treatment of the first relapse. Therefore the efficacy of I plus HU was analysed in a phase II study in GBM pts before progression was confirmed. As the role of enzyme-inducing anticonvulsive drugs in this setting is not clear only non-enzyme-inducing anticonvulsive drugs were allowed in this study.

Methods: From 2003, December up to 2005, June 30 non-progressive GBM pts were included, all of them in a phase of stable disease for more than 6 weeks following effective primary or secondary treatment after the first relapse including surgery, radiotherapie and at least one chemotherapeutic regimen. No enzyme-inducing anticonvulsive drugs were allowed. 600 mg of I and 1000 mg of HU were given as a continuous daily dosage, all pts were followed up by blood cell count weekly and magnetic resonance imaging every 6 weeks.

Results: All pts are eligible for toxicity and 28 pts for 6 months progression free survival (PFS) and 6 months overall survival (OS), 25 pts are male, 5 pts female, the median age is 44 years (32 to 71). All 30 pts had prior radiotherapy, 21 pts had temozolomide containing chemotherapy and 9 pts not temozolomide containing regimens only. The median observation time is 13 months. 6 months PFS is 64% (18/28) and 6 months is OS 93 % (26/28) so fare. Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts (anemia grade 3: 2 pt; anemia grade 2: 4 pts; leucocytopenia grade 3: 2 pts; leucocytopenia grade 2: 7 pts; thrombocytopenia grade 2: 4 pts) and required dose reduction of HU in 8 pts, dosereduction of I in 1 pt and G-CSF subcutaniously in 8 pts. There was no febrile neutropenia, no interruption of the study due to toxicity and no treatment related death.

Conclusion: In the examined regimen the combination of I (600 mg / day) and HU (1000 mg / day) was feasible but showed a significant higher rate of hematotoxicity compared to the combination with I 400 mg daily. The 6 months PFS and OS data are promising, observation time, however, is short. Efficacy and toxicity data of the entire group of pts will be updated for the DKK 2006.