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Leary SES, Lindsay K, Geyer JR, et al. Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026). Neuro Oncol. 2021;doi: 10.1093/neuonc/noab293.
Leary, S. E. S., Lindsay, K., Geyer, J. R., Mehmet, K., Huang, J., Smith, K. S., Hadley, J., Ermoian, R., MacDonald, T. J., Goldman, S., Phillips, P., Young Poussaint, T., Olson, J. M., Ellison, D. W., Dunkel, I. J., Fouladi, M., Onar-Thomas, A., & Northcott, P. A. (2021). Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026). Neuro-oncology, . https://doi.org/10.1093/neuonc/noab293
Leary, Sarah E S, et al. "Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026)." Neuro-oncology vol. (2021). doi: https://doi.org/10.1093/neuonc/noab293
Leary SES, Lindsay K, Geyer JR, Mehmet K, Huang J, Smith KS, Hadley J, Ermoian R, MacDonald TJ, Goldman S, Phillips P, Young Poussaint T, Olson JM, Ellison DW, Dunkel IJ, Fouladi M, Onar-Thomas A, Northcott PA. Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026). Neuro Oncol. 2021 Dec 22; doi: 10.1093/neuonc/noab293. Epub 2021 Dec 22. PMID: 34935967.
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Neuro Oncol. 2021 Dec 22; doi: 10.1093/neuonc/noab293. Epub 2021 Dec 22.

Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026).

Neuro-oncology

Sarah E S Leary, Kilburn Lindsay, J Russell Geyer, Kocak Mehmet, Jie Huang, Kyle S Smith, Jennifer Hadley, Ralph Ermoian, Tobey J MacDonald, Stewart Goldman, Peter Phillips, Tina Young Poussaint, James M Olson, David W Ellison, Ira J Dunkel, Maryam Fouladi, Arzu Onar-Thomas, Paul A Northcott

Affiliations

  1. Cancer and Blood Disorders Center, Seattle Children's, University of Washington, Fred Hutchinson Cancer Research Center.
  2. Center for Cancer and Blood Disorders, Children's National Hospital.
  3. Department of Biostatistics, St. Jude Children's Research Hospital.
  4. Department of Developmental Neurobiology, St. Jude Children's Research Hospital.
  5. Department of Radiation Oncology, University of Washington.
  6. Aflac Cancer and Blood Disorders Center, Emory University.
  7. Department of Child Health, Phoenix Children's Hospital.
  8. Pediatric Oncology, Children's Hospital of Philadelphia.
  9. Department of Radiology, Boston Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School.
  10. Department of Pathology, St. Jude Children's Research Hospital.
  11. Department of Pediatrics, Memorial Sloan Kettering Cancer Center.
  12. Pediatric Hematology & Oncology, Nationwide Children's Hospital.

PMID: 34935967 DOI: 10.1093/neuonc/noab293

Abstract

BACKGROUND: Embryonal tumors of the CNS are the most common malignant tumors occurring in the first years of life. This study evaluated the feasibility and safety of incorporating novel non-cytotoxic therapy with vorinostat and isotretinoin to an intensive cytotoxic chemotherapy backbone.

METHODS: PBTC-026 was a prospective multi-institutional clinical trial for children < 48 months of age with newly diagnosed embryonal tumors of the CNS. Treatment included three 21-day cycles of induction therapy with vorinostat and isotretinoin, cisplatin, vincristine, cyclophosphamide, and etoposide; three 28-day cycles of consolidation therapy with carboplatin and thiotepa followed by stem cell rescue; and twelve 28-day cycles of maintenance therapy with vorinostat and isotretinoin. Patients with M0 medulloblastoma received focal radiation following consolidation therapy. Molecular classification was by DNA methylation.

RESULTS: Thirty-one patients with median age 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was medulloblastoma (MB) in 20 and supratentorial CNS embryonal tumor in 11. 24/31 patients completed induction therapy within a pre-specified feasibility window of 98 days. Five-year progression free (PFS) and overall survival (OS) for all 31 patients was 55 + 15 and 61 + 13, respectively. Five-year PFS was 42 + 13 for Group 3 MB (n=12); 80 + 25 for SHH MB (n=5); 33 + 19 for Embryonal Tumor with Multilayered Rosettes (ETMR, n=6).

CONCLUSION: It was safe and feasible to incorporate vorinostat and isotretinoin into an intensive chemotherapy regimen. Further study to define efficacy in this high-risk group of patients is warranted.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Keywords: CNS embryonal tumor; medulloblastoma; pediatric brain tumor; vorinostat

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