Low-grade glioma, pediatric

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

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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.
6 regimens on this page
10 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

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 NR 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

Chemotherapy

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

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

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed NCT00002944
  3. 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 contains dosing details in manuscript PubMed

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

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

42-day cycle for 10 cycles


Regimen variant #3, 12 cycles

Study Dates of enrollment Evidence
Packer et al. 1993 NR Non-randomized

Preceding treatment

  • Adjuvant CV

Chemotherapy

42-day cycle for 12 cycles

References

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed NCT00002944
  3. 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 contains dosing details in manuscript PubMed

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 Inferior ORR

Biomarker eligibility criteria

  • BRAF V600 mutation

Chemotherapy

10-week course

References

  1. 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 refers to dosing details in COG A9952 PubMed NCT02684058

Cisplatin & Etoposide (EP)

Regimen

Study Evidence
Massimino et al. 2010 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

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

  1. 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 contains dosing details in manuscript PubMed

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 Superior 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

  1. 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 contains dosing details in manuscript PubMed 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

28-day cycle for 11 cycles


Regimen variant #2

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

Chemotherapy

28-day cycle for 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