Vorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026). Issue 7 (22nd December 2021)

• Record Type: Journal Article
• Authors: Leary, Sarah E S; Kilburn, Lindsay; Geyer, J Russell; Kocak, Mehmet; Huang, Jie; Smith, Kyle S; Hadley, Jennifer; Ermoian, Ralph; MacDonald, Tobey J; Goldman, Stewart; Phillips, Peter; Young Poussaint, Tina; Olson, James M; Ellison, David W; Dunkel, Ira J; Fouladi, Maryam; Onar-Thomas, Arzu; Northcott, Paul A
• Is Part Of: Neuro-oncology. Volume 24:Issue 7(2022)
• Page Start: 1178
• Page End: 1190
• Publication Date: 2021-12-22
• Subjects: CNS embryonal tumor -- medulloblastoma -- pediatric brain tumor -- vorinostat; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab293
• Languages: English
• ISSNs: 1522-8517

Abstract

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 (MB) received focal radiation following consolidation therapy. Molecular classification was by DNA methylation array. Results: Thirty-one patients with median age of 26 months (range 6-46) received treatment on study; 19 (61%) were male. Diagnosis was 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 survival (PFS) and overall survival (OS) for all 31 patients were 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.