Imatinib mesylate in the treatment of patients with recurrent high grade gliomas expressing PDGF-R

Abstract

1526 Background: Despite noticeable progress in the treatment of high-grade gliomas (HGG), most patients experience tumor recurrence after standard treatment consisting of surgery, radiotherapy and concomitant chemotherapy. Imatinib mesylate, a tyrosine kinase inhibitor of PDGFR-α, -β, c-kit, abl and arg, has been shown to produce tumor response in patients with recurrent gliomas (Raymond ProcASCO 2004, Dresemann ProcASCO 2004&2005, Reardon Proc ASCO 2005). We treated 34 patients with recurrent HGGs showing immunohistochemical expression of “imatinib targets” in the tumor tissue with imatinib. Methods: 34 patients, 16 women, 18 men, aged from 27 to 72 years, in median 49 years with recurrent HGG (GBM n= 23, AA n=11) were treated with imatinib 400 mg/day as continuous daily oral dosing. MRI was performed every three months or at clinical suspicion of progression. The median interval from diagnosis to the start of imatinib was 12.6 months (range 4.3 to 143 months). Imatinib was the 2nd line therapy in 15 patients, 3rd line in 13 and 4th line in 6 patients. ECOG performance score at start of imatinib was 1 in 9, 2 in 21 and 3 in 4 patients, respectively.Immunohistochemical analysis was performed on formalin fixed and paraffin embedded tumor tissue with antibodies against PDGFR-α, and -β. Results: The median treatment period with imatinib was 4 months (3 weeks to 17 months). The best response achieved was major response in 2 patients, partial remission in 6, stable disease in 12 and progressive disease in 14 patients. Eleven patients were free from tumor progression after 6 months (PFS-6 32,4%). The two patients with major response improved clinically and showed no more evidence of increased metabolism as well in MRI spectroscopy as in C11-methionine PET for 13 and 17 months, respectively. One of them showed widespread PDGF-R-α expression in the tumor tissue. In all patients with objective response to imatinib, a clinical benefit was noted within the first month of treatment. Conclusions: Compared to the results of Raymond et al, we observed a higher percentage of patients with progression free survival at 6 months. Detailed analysis of imatinib targets in tumor tissue of patients treated with imatinib will be helpful to explore the potential of imatinib as treatment option for patients with HGG. No significant financial relationships to disclose.