P05.03 EFFECT OF COMBINED THERAPY WITH BEVACIZUMAB AND TEMOZOLOMIDE (TMZ) IN PEDIATRIC MALIGNANT GLIOMAS (MG)

METHOD: There were 19 pts with MG, who enrolled in the study from May 2010 till March 2014 (10 boys and 9 girls), median age 9 yrs (range, 3-17 yrs). 15 pts (79%) were with glioblastoma (GB), 4 (21%) - anaplastic astrocytoma (AA). In 16 pts the tumor was localized supratentorial (84.21%), in 3 - infratentorial (15.79%). All pts received resection of the tumor (total resection was detected in 3 pts (15.79%), subtotal in 13 pts (68.43%), partial in 2 pts (10.52%), biopsy 1 pts (5.26%)), local radiation therapy (RT) 55 Gy with parallel chemotherapy (CT): TMZ 75 mg/m2 p.o. everyday + Bevacizumab 5 mg/kg i.v. every 2 weeks (twice), followed by 6 cycles of combined CT: TMZ 150-200 mg/m2 (1-5 days) + Bevacizumab 5 mg/kg every 2 weeks, followed by maintain therapy for two years with Bevacizumab 15 mg/kg every 3 weeks. In 3 patients due to residual tumor after CT and 2 patients due to residual tumor after maintain therapy the stereotactic radiosurgery (gamma knife) was performed. RESULTS: For the analyzed moment 13 pts are still alive (68.42%), 6 pts with PD died (31.58%). 4-years PFS/OS in all pts is 0,58 plus or minus 0.11/0,68 plus or minus 0.11. Median of observing time - 39 months (range, 12-53). After RT the objective response observed in all 19 pts: CR 5 (26.32%), PR 11 (57.89%), SD 3 (15.79%). All 19 pts received combined therapy TMZ + Bevacizumab (18 pts - 6 cycles and 1pt - only 4 cycles). The objective response after combined CT was: CR 7 (36.85%), PR 2 (10.52%), SD 4 (21.05%), PD 6 (31.58%). 13 pts received maintain therapy with Bevacizumab. Median of number of cycles for 1 pt was 22 (range 4-22). The objective response after combined CT was: CR 9 (69.42%), SD 2 (15.38%), PD 2 (15.38%). 4-years PFS was better in pts older 5 years vs under 5 years - 0.62 and 0.33, respectively (p = 0.50), in boys vs girls - 0.67 and 0.37, respectively (p = 0.50), in pts with supratentorial localization vs infratentorial - 0.60 and 0.33, respectively (p = 0.58), in pts with total resection vs subtotal - 0.67 and 0.56, respectively (p = 0.88), in pts with AA vs GB - 0,75 and 0.53, respectively (p = 0.53). CONCLUSION: The combined therapy with Bevacizumab and TMZ after resection tumor is an effective strategy in children with AA and GB.