title: Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system.
abstract: BACKGROUND
  The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug delivery to the CNS.
  
  
  METHODS
  Data of patients treated with carboplatin or methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity.
  
  
  RESULTS
  Fifty-four patients were treated. Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status > or =70% (P = .0013 and .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P = .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia.
  
  
  CONCLUSIONS
  Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long-term survival may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
authors: Kristoph
authors: K
authors: Jahnke
authors: Dale F
authors: DF
authors: Kraemer
authors: Kristin R
authors: KR
authors: Knight
authors: David
authors: D
authors: Fortin
authors: Susan
authors: S
authors: Bell
authors: Nancy D
authors: ND
authors: Doolittle
authors: Leslie L
authors: LL
authors: Muldoon
authors: Edward A
authors: EA
authors: Neuwelt
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D007261:Infusions, Intra-Arterial / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000532:radiotherapy; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D008727:Methotrexate