title: Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme.
abstract: A phase II study was conducted to assess the efficacy of administering daily thalidomide concomitantly with radiation and continuing for up to 1 year following radiation in children with brain stem gliomas (BSG) or glioblastoma multiforme (GBM). Secondary objectives were to obtain preliminary evidence of biologic activity of thalidomide and to evaluate toxicities from chronic administration of thalidomide in this population. Thirteen patients (2-14 years old) with newly diagnosed BSG (12 patients) or GBM (one patient) were enrolled between July 1999 and June 2000. All patients received focal radiotherapy to a total dose of 5,580 cGy. Thalidomide was administered once daily beginning on the first day of radiation and continued for 12 months or until the patient came off study. The starting dose was 12 mg/kg (rounded down to the nearest 50 mg) and was increased by 20% weekly, if tolerated, to 24 mg/kg or 1,000 mg (whichever was lower). Advanced imaging techniques and urine and serum analysis for anti-angiogenic markers were performed in some patients in an attempt to correlate changes with clinical effect of therapy. No patients completed the planned 12 months of thalidomide therapy and all have since died of disease progression. The median duration of therapy was 5 months (range 2-11 months). Nine patients came off study for progressive disease (PD), three patients due to toxicity and one patient withdrew consent. Several patients on this study required more extended courses of high dose steroids than would have been otherwise expected for this population due to significant peritumoral edema and necrosis. No consistent pattern emerged from the biologic correlative studies from 11 patients. However, advanced imaging with techniques such as MR spectroscopy, MR perfusion and 18-fluorodeoxyglucose positron emission tomography (FDG-PET) were helpful in distinguishing growing tumor from treatment effect and necrosis in some patients. The median time to progression (TTP) was 5 months (range 2-11 months) and the median time to death (TTD) was 9 months (range 5-17 months). In this small patient sample adding thalidomide to radiation did not improve TTP or TTD from historical controls, however, toxicity appeared to be increased.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. christopher_turner@dfci.harvard.edu
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Turner
authors.forename: Susan
authors.initials: S
authors.lastname: Chi
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Marcus
authors.forename: Tobey
authors.initials: T
authors.lastname: MacDonald
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Sridhar
authors.initials: S
authors.lastname: Vajapeyam
authors.forename: Nicole
authors.initials: N
authors.lastname: Ullrich
authors.forename: Liliana C
authors.initials: LC
authors.lastname: Goumnerova
authors.forename: R Michael
authors.initials: RM
authors.lastname: Scott
authors.forename: Caitlin
authors.initials: C
authors.lastname: Briody
authors.forename: Christine
authors.initials: C
authors.lastname: Chordas
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Zimmerman
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D013792:Thalidomide / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide