High-grade glioma, pediatric

Section editor
	Nicole M. Wood, DO University of Missouri Kansas City, MO, USA LinkedIn

This page contains studies that are specific to pediatric populations.

• For the more general high-grade glioma category page, follow this link.
• For pediatric low-grade glioma (pLGG), follow this link.

4 regimens on this page 5 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

• NCCN Guidelines - Pediatric Central Nervous System Cancers

Adjuvant therapy

Temozolomide & RT

Temozolomide & RT: Temozolomide & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Grill et al. 2018 (HERBY)	2011-2015	Randomized Phase 2 (C)	Temozolomide, Bevacizumab, RT	Did not meet primary endpoint of EFS

Preceding treatment

• Surgical biopsy, partial resection, or total resection

Chemotherapy

• Temozolomide (Temodar) as follows:
  • Cycle 1 (chemoradiation): 75 mg/m² PO or IV once per day on days 1 to 42
  • Cycles 2 to 13: 150 to 200 mg/m² PO once per day on days 1 to 5

Radiotherapy

• Concurrent radiation therapy as follows:
  • Cycle 1: 180 cGy fractions x 30 fractions, for a total dose of 5400 cGy

10-week course, then 28-day cycle for up to 12 cycles

References

1. HERBY: Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, Le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G. Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol. 2018 Apr 1;36(10):951-958. Epub 2018 Feb 7. link to original article contains dosing details in manuscript PubMed NCT01390948

VCP

VCP: Vincristine, CCNU (Lomustine), Prednisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Finlay et al. 1995 (CCG-945)	1985-1990	Phase 3 (C)	8-drug regimen	Did not meet primary endpoint of OS

Note: the exact schedule of vincristine is impossible to discern from Figure 1.

Preceding treatment

• Surgery, then adjuvant Vincristine & RT

Chemotherapy

• Lomustine (CCNU) 100 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

42-day cycle for 8 cycles

References

1. CCG-945: Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M, Turski PA, Wara WM, Edwards M, Sutton LN, Berger MS, Epstein F, Ayers G, Allen JC, Packer RJ; Children's Cancer Group. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. J Clin Oncol. 1995 Jan;13(1):112-23. link to original article contains dosing details in manuscript PubMed

Vincristine & RT

Vincristine & RT: Vincristine & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Finlay et al. 1995 (CCG-945)	1985-1990	Phase 3 (C)	8-drug regimen	Did not meet primary endpoint of OS

Preceding treatment

• Surgery

Chemotherapy

• Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64

Radiotherapy

• Concurrent radiation therapy

70-day course

Subsequent treatment

• Adjuvant VCP

References

1. CCG-945: Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M, Turski PA, Wara WM, Edwards M, Sutton LN, Berger MS, Epstein F, Ayers G, Allen JC, Packer RJ; Children's Cancer Group. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. J Clin Oncol. 1995 Jan;13(1):112-23. link to original article contains dosing details in manuscript PubMed

Recurrent disease, non-curative therapy, non-randomized or retrospective data

Temozolomide monotherapy

Regimen variant #1, no radiation history

Study	Dates of enrollment	Evidence
Nicholson et al. 2007	1998-1999	Non-randomized

Chemotherapy

• Temozolomide (Temodar) 150 to 200 mg/m² PO once per day on days 1 to 5
  • Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m² PO once per day on days 1 to 5

28-day cycle for up to 11 cycles

Regimen variant #2, previous craniospinal irradiation (CSI)

Study	Dates of enrollment	Evidence
Nicholson et al. 2007	1998-1999	Non-randomized

Chemotherapy

• Temozolomide (Temodar) 180 mg/m² PO once per day on days 1 to 5

28-day cycle for up to 11 cycles

References

1. Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH; Children's Oncology Group. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. link to original article contains dosing details in manuscript PubMed