title: Alisertib is active as single agent in recurrent atypical teratoid rhabdoid tumors in 4 children.
abstract: BACKGROUND
  Aurora Kinase A (AURKA) encodes a protein that regulates the formation and stability of the mitotic spindle and is highly active in atypical teratoid rhabdoid tumors (ATRT) through loss of the INI1 tumor suppressor gene. Alisertib (MLN8237) inhibits AURKA in vitro and in vivo. Given the strong preclinical data supporting the use of alisertib for ATRT patients, we sought and obtained permission to use alisertib in single patient treatment plans for 4 recurrent pediatric ATRT patients.
  
  
  METHODS
  Patients with recurrent or progressive ATRT received alisertib 80 mg/m(2) by mouth once daily for 7 days of a 21-day treatment cycle. Disease evaluation (MRI of brain and spine and lumbar puncture) was done after 2 cycles of alisertib and every 2-3 cycles thereafter for as long as the patients remained free from tumor progression.
  
  
  RESULTS
  Four patients with median age of 2.5 years (range, 1.39-4.87 y) at diagnosis received alisertib 80 mg/m(2) by mouth once daily for 7 days of a 21-day treatment cycle, and all 4 patients had disease stabilization and/or regression after 3 cycles of alisertib therapy. Two patients continued to have stable disease regression for 1 and 2 years, respectively, on therapy.
  
  
  CONCLUSIONS
  Single-agent alisertib produced marked and durable regression in disease burden, as detected by brain and spine MRI and by evaluation of spinal fluid cytology. Alisertib has moderate but manageable toxicities, and its chronic administration appears feasible in this pediatric population. These novel data support the incorporation of alisertib in future therapeutic trials for children with ATRT.
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Cynthia
authors: C
authors: Wetmore
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: James
authors: J
authors: Boyett
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Shaoyu
authors: S
authors: Li
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Tong
authors: T
authors: Lin
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Anne
authors: A
authors: Bendel
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Amar
authors: A
authors: Gajjar
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (C.W., A.G.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (J.B., S.L., T.L.); Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota (A.B.); Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee (B.A.O.).
authors: Brent A
authors: BA
authors: Orr
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000378:metabolism; D001381:Azepines / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D018335:Rhabdoid Tumor / Q000188:drug therapy* / Q000378:metabolism; D013724:Teratoma / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; C550258:MLN 8237; D011743:Pyrimidines; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: ATRT; Aurora kinase A; brain tumor; pediatric; targeted therapy