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

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.

Automated summary

This study evaluated the feasibility and safety of incorporating vorinostat and isotretinoin into an intensive chemotherapy regimen for embryonal tumors of the CNS. The results showed that this combination therapy is safe and feasible, and further study is needed to determine its efficacy in high-risk patients.