Chemotherapy for High-Grade Gliomas in Children

Treatment

• Temozolomide plus radiation: The combination of temozolomide and radiation is superior to radiation alone. The Stupp protocol is the standard backbone of therapy for HGGs , superseding the previous lomustine-based therapy (31). It is much better tolerated. It consists of temozolomide, 90 mg/ m2/dose, orally for 42 days during radiation; then temozolomide, 200 mg/ m2/dose, orally for 5 days of 28-day cycles for 12 months.
• Bevacizumab for recurrent glioblastomas: Bevacizumab has been shown to improve the quality of life for children with recurrent glioblastomas by significantly delaying the need for steroids, thereby avoiding the complications that accompany steroid use in recurrent disease. Bevacizumab is given at a rate of 10 mg/kg IV every 2 weeks and has FDA and Health Canada approval: Bevacizumab has also been demonstrated to be beneficial in cases of radiation necrosis (32). The role of bevacizumab for treatment of newly diagnosed HGGs during radiation and during maintenance is being explored in clinical trials.

Infants

• Intensive chemotherapy alone: Cure or delay of radiation is possible in young children, especially those under 12 months of age, if they go into consolidation chemotherapy with no residual disease. There can be a gross total resection at diagnosis, or a two-stage surgical resection can be used with the initial surgery at diagnosis followed by a repeat surgery after two to four cycles of induction chemotherapy when it is felt that such an approach will reduce postoperative complications.

Adjuvant Therapy

• Radiation: Involved field usually as dissemination is uncommon, and it is local control that is problematic.
• Immunotherapy: Immunotherapy is being evaluated in clinical trials only.

Complications

• Pneumocystis infection: Pneumocystis infection is a risk from the start of radiation, and therefore prophylaxis is required. Since there have been reports of prolonged thrombocytopenia and death due to low-dose, prolonged temozolomide treatment, trimethoprim/sulfamethoxazole is not recommended for use in protecting against Pneumocystis infection in these children. Rather, monthly inhaled or IV pentamidine or an appropriate alternative should be used.
• Wound healing problems: Bevacizumab interferes with wound healing. Therefore, the initiation of bevacizumab should be delayed for 4 weeks following major surgery. Also due to increased skin breakdown with concomitant steroids, their concomitant prolonged use should be avoided.

Outcome

• 24–50% 5-year survival rate: The 5-year overall survival rate for patients with anaplastic astrocytomas is about 50%. The 5-year survival rate for patients with glioblastomas is 24% for those with MGMT methylation but less than 10% for those that are unmethylated. Gross total resection has a significant impact on survival.