ИСТИНА

The survival rate of children with primary high grade CNS-gliomas (HGG) remains low. There are no effective chemotherapeutic regimens for pediatric HGG. Recent studies have shown the effectiveness of Bevacizumab & Temozolomide combination in adults. The aim of our study was to evaluate the effect of this approach in increasing overall survival (OS) in children with CNS-HGGs. PATIENTS AND METHODS. In a prospective study, from January 2009 to December 2016, we observed the group of 25 children aged 2 – 17 years (males – 16, females – 9) with anaplastic astrocytoma (n=11) and glioblastoma (n=14) of CNS. After surgery all patients received local radiotherapy (RT) in dose 55-60 Gy combined with Temozolomide 75 mg/m2 daily from the first day of RT. Following RT patients received 6-12 cycles of combined therapy which consisted of Temozolomide 150 mg/m2 orally, on days 1-5 and Bevacizumab 5 mg/kg intravenously, on days 1 and 15, repeated every 28-days. Follow up therapy included Bevacizumab in dose (5 mg/kg) every 21 days during 12 months. The primary end point was progression-free survival; secondary end points were overall survival and safety. RESULTS. Response assessment showed that 6/25 (24%) achieved complete response (PR), 8/25 (32%) – partial response (PR) and 11/25 (44%) – stable disease (SD). The median PFS was 19,5 months. The -12, 24, -36 and 48-month PFS were 65±14%, 44±16%, 32±12% and 28±10%, respectively. The median OS was 24,5 months. The -12, 24, 36 and 48-month OS were 73±13%, 46±15%, 39±12% and 34±10%, respectively. The therapy was well tolerated with low toxicity. Grade 3 thrombocytopenia related to Temozolomide was noted in 10 patients, grade 2 proteinuria – in 2, and intratumoral hemorrhage – in 1. Conclusion. The combination of Bevacizumab and Temozolomide in children with primary HGGs, resulted in increased PFS and OS and better tolerance compared to historical data (24-month PFS and OS in patients treated by surgery, simultaneous radiochemotherapy with radiotherapy and a 5-6 weeks course of oral temozolomide at 75 mg/m2/d followed by additional 12 cycles of oral temozolomide given as a 5 day course at 150-200 mg/m2/d every 28 days in our group was 28±9% and 31±10%).