Low-grade glioma, pediatric

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This page contains studies that are specific to pediatric populations. 
*For the more general low-grade glioma category page, follow this link.
*For pediatric high-grade glioma (pHGG), follow this link.
Last updated on 2024-07-23:7 regimens on this page
11 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=
==Carboplatin & Vincristine==
CV: Carboplatin & Vincristine
VC: Vincristine & Carboplatin
===Regimen variant #1, 175/1.5 (capped vincristine)===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Packer et al. 1993 	Not reported 	Non-randomized	 	
Ater et al. 2012 (COG A9952)	1997-2005 	Phase 3 (C) 	TPCV 	Did not meet co-primary endpoints of EFS/OS
Note: The course begins on day 0.
====Preceding treatment====
*Biopsy or incomplete resection
====Chemotherapy====
*Carboplatin (Paraplatin) 175 mg/m2 IV once per day on days 0, 7, 14, 21, 42, 49, 56, 63
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63
10-week course
====Subsequent treatment====
*CV consolidation
===Regimen variant #2, 550/1.5 (uncapped vincristine)===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Gnekow et al. 2017 (SIOP-LCG 2004)	2004-2012 	Phase 3 (C)	VCE 	Did not meet primary endpoint of PFS
====Preceding treatment====
*Biopsy or incomplete resection
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: 550 mg/m2 IV over 60 minutes once on day 1
**Cycles 5 to 7: 550 mg/m2 IV over 60 minutes once on day 1
*Vincristine (Oncovin) as follows:
**Cycles 1 to 4: 1.5 mg/m2 IV once per day on days 1, 8, 15
**Cycles 5 to 7: 1.5 mg/m2 IV once on day 1
21-day cycle for 4 cycles, then 28-day cycle for 3 cycles
====Subsequent treatment====
*CV consolidation
===References===
# Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, Phillips PC, Ryan J, Boyett JM, Geyer R, Finlay J. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993 May;11(5):850-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# COG A9952: Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2641-7. Epub 2012 Jun 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002944
# SIOP-LGG 2004: Gnekow AK, Walker DA, Kandels D, Picton S, Perilongo G, Grill J, Stokland T, Sandstrom PE, Warmuth-Metz M, Pietsch T, Giangaspero F, Schmidt R, Faldum A, Kilmartin D, De Paoli A, De Salvo GL; of the Low Grade Glioma Consortium and the participating centers. A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - a final report. Eur J Cancer. 2017 Aug;81:206-225. Epub 2017 Jun 22. Erratum in: Eur J Cancer. 2017 Dec 13;:. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC EudraCT 2005-005377-29
# LOGGIC/​FIREFLY-2: NCT05566795
=Consolidation after adjuvant therapy=
==Carboplatin & Vincristine==
CV: Carboplatin & Vincristine
===Regimen variant #1, 8 cycles===
Study 	Dates of enrollment	Evidence
Ater et al. 2012 (COG A9952)	1997-2005 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Adjuvant CV
====Chemotherapy====
*Carboplatin (Paraplatin) 175 mg/m2 IV once per day on days 1, 8, 15, 22
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
42-day cycle for 8 cycles
===Regimen variant #2, 10 cycles===
Study 	Dates of enrollment	Evidence
Gnekow et al. 2017 (SIOP-LCG 2004)	2004-2012 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Adjuvant CV
====Chemotherapy====
*Carboplatin (Paraplatin) 550 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15
42-day cycle for 10 cycles
===Regimen variant #3, 12 cycles===
Study 	Dates of enrollment	Evidence
Packer et al. 1993	Not reported 	Non-randomized
====Preceding treatment====
*Adjuvant CV
====Chemotherapy====
*Carboplatin (Paraplatin) 175 mg/m2 IV once per day on days 1, 8, 15, 22
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
42-day cycle for 12 cycles
===References===
# Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, Phillips PC, Ryan J, Boyett JM, Geyer R, Finlay J. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993 May;11(5):850-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# COG A9952: Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2641-7. Epub 2012 Jun 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002944
# SIOP-LGG 2004: Gnekow AK, Walker DA, Kandels D, Picton S, Perilongo G, Grill J, Stokland T, Sandstrom PE, Warmuth-Metz M, Pietsch T, Giangaspero F, Schmidt R, Faldum A, Kilmartin D, De Paoli A, De Salvo GL; of the Low Grade Glioma Consortium and the participating centers. A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - a final report. Eur J Cancer. 2017 Aug;81:206-225. Epub 2017 Jun 22. Erratum in: Eur J Cancer. 2017 Dec 13;:. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
=Recurrent or progressive, non-curative therapy=
==Carboplatin & Vincristine==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Bouffet et al. 2023 (TADPOLE)	2017-2021 	Randomized Phase 2 (C)	Dabrafenib & Trametinib	Lower ORR
====Biomarker eligibility criteria====
*BRAF V600 mutation
====Chemotherapy====
*Carboplatin (Paraplatin) 175 mg/m2 IV once per day on days 0, 7, 14, 21, 42, 49, 56, 63
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63
10-week course
===References===
#TADPOLE: Bouffet E, Hansford JR, Garrè ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, van der Lugt J, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Bento Pereira da Silva A, Russo M, Hargrave DR. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023 Sep 21;389(12):1108-1120. link to original article does not contain dosing details in manuscript; refers to COG A9952 EuroPMC NCT02684058
==Cisplatin & Etoposide (EP)==
===Regimen===
Study 	Dates of enrollment	Evidence
Massimino et al. 2010	2001-11 to 2007-12 	Non-randomized
Note: In children less than 1 year old or less than 10 kg, "doses were adjusted to their weight"--reference does not say exactly how doses are adjusted.
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV over 2 hours once per day on days 1 to 3, given first
*Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once per day on days 1 to 3, given second
====Supportive therapy====
*Hydration for 2 hours before chemotherapy, and for 2 hours after chemotherapy
28-day cycle for 4 cycles, then 35-day cycle for 3 cycles, then 42-day cycle for 3 cycles
===References===
# Massimino M, Spreafico F, Riva D, Biassoni V, Poggi G, Solero C, Gandola L, Genitori L, Modena P, Simonetti F, Potepan P, Casanova M, Meazza C, Clerici CA, Catania S, Sardi I, Giangaspero F. A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neurooncol. 2010 Oct;100(1):65-71. Epub 2010 Feb 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Dabrafenib & Trametinib==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Bouffet et al. 2023 (TADPOLE)	2017-2021 	Randomized Phase 2 (E-RT-switch-ooc)	Carboplatin & Vincristine	Higher ORR (primary endpoint)ORR: 47% vs 11%(RR 4.31, 95% CI 1.7-11.2)
====Biomarker eligibility criteria====
*BRAF V600 mutation
====Targeted therapy====
*Dabrafenib (Tafinlar) by the following age-based criteria:
**Less than 12 years old: 2.625 mg/kg PO twice per day
**12 years or older: 2.25 mg/kg PO twice per day 
*Trametinib (Mekinist) by the following age-based criteria:
**Less than 6 years old: 0.032 mg/kg PO once per day
**6 years or older: 0.025 mg/kg PO once per day
Continued indefinitely
===References===
#TADPOLE: Bouffet E, Hansford JR, Garrè ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, van der Lugt J, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Bento Pereira da Silva A, Russo M, Hargrave DR. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023 Sep 21;389(12):1108-1120. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02684058
==Temozolomide monotherapy==
===Regimen variant #1===
Study 	Dates of enrollment	Evidence
Nicholson et al. 2007	1998-1999 	Non-randomized
Note: This dosing is for patients who previously received craniospinal irradiation (CSI).
====Chemotherapy====
*Temozolomide (Temodar) 180 mg/m2 PO once per day on days 1 to 5
28-day cycle for 11 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Nicholson et al. 2007	1998-1999 	Non-randomized
====Chemotherapy====
*Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for 11 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Tovorafenib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kilburn et al. 2023 (FIREFLY-1)	2021-2022 	Phase 2 (RT)
Note: This was the RP2D reported in the manuscript. The FDA-recommended dose is 380 mg/m2 (maximum dose of 600 mg).
====Biomarker eligibility criteria====
*BRAF alteration
====Prior treatment criteria====
*At least one line of prior systemic therapy
====Targeted therapy====
*Tovorafenib (Ojemda) 420 mg/m2 (maximum dose of 600 mg) PO once on day 1
7-day cycles
===References===
#FIREFLY-1: Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024 Jan;30(1):207-217. Epub 2023 Nov 17. Erratum in: Nat Med. 2024 May;30(5):1500. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04775485
Category:Low-grade glioma regimens
Category:Disease-specific pages
Category:Low-grade gliomas
Category:Pediatric neurologic neoplasms