Journal of Neuro-Oncology

, Volume 82, Issue 1, pp 95–101 | Cite as

Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme

  • Christopher D. TurnerEmail author
  • Susan Chi
  • Karen J. Marcus
  • Tobey MacDonald
  • Roger J. Packer
  • Tina Young Poussaint
  • Sridhar Vajapeyam
  • Nicole Ullrich
  • Liliana C. Goumnerova
  • R. Michael Scott
  • Caitlin Briody
  • Christine Chordas
  • Mary Ann Zimmerman
  • Mark W. Kieran
Clinical–Patient Studies


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.


Thalidomide Radiation therapy Children Brain stem glioma Glioblastoma multiforme Advanced MR techniques Biologic correlative studies 



Dana-Farber/Children’s Hospital Cancer Center


Children’s National Medical Center


Glioblastoma multiforme


Brain stem glioma


Lactate dehydrogenase


Progressive disease


Stable disease


Partial response


Complete response


Basic fibroblastic growth factor


Platelet derived growth factor


Vascular endothelial growth factor


System for Thalidomide Education and Prescribing Safety


18-Fluorodeoxyglucose positron emission tomography


Time to progression


Time to death



A preliminary report of data from this study was presented in part at the Tenth International Symposium for Pediatric Neuro-Oncology in June 2002. Support for this study was provided through the Stop & Shop Family Pediatric Brain Tumor Program. Costs of data management were supported by Celgene Pharmaceuticals Corporation.


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Christopher D. Turner
    • 1
    Email author
  • Susan Chi
    • 1
  • Karen J. Marcus
    • 2
  • Tobey MacDonald
    • 3
  • Roger J. Packer
    • 3
  • Tina Young Poussaint
    • 4
  • Sridhar Vajapeyam
    • 4
  • Nicole Ullrich
    • 5
  • Liliana C. Goumnerova
    • 6
  • R. Michael Scott
    • 6
  • Caitlin Briody
    • 1
  • Christine Chordas
    • 1
  • Mary Ann Zimmerman
    • 1
  • Mark W. Kieran
    • 1
  1. 1.Department of Pediatric OncologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Department of MedicineDivision of Radiation Oncology, Children’s Hospital BostonBostonUSA
  3. 3.Departments of Neurology and Hematology/OncologyChildren’s National Medical CenterWashingtonUSA
  4. 4.Department of RadiologyChildren’s Hospital BostonBostonUSA
  5. 5.Department of NeurologyChildren’s Hospital BostonBostonUSA
  6. 6.Department of NeurosurgeryChildren’s Hospital BostonBostonUSA

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