isotretinoin and Neoplasms--Germ-Cell-and-Embryonal

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.. 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.. 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).. 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.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cerebellar Neoplasms; Child; Child, Preschool; Cyclophosphamide; Etoposide; Female; Humans; Infant; Isotretinoin; Male; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Neuroectodermal Tumors, Primitive; Prospective Studies; Vincristine; Vorinostat

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.

Topics: Autografts; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Child, Preschool; Chromosomes, Human, Pair 19; Female; Genetic Loci; Humans; Isotretinoin; Neoplasms, Germ Cell and Embryonal; Stem Cell Transplantation; Vorinostat

Topics: Adolescent; Adult; Drug Evaluation; Humans; Isotretinoin; Male; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Tretinoin