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

  • Clinical–Patient Studies
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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.

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Abbreviations

DFCHCC:

Dana-Farber/Children’s Hospital Cancer Center

CNMC:

Children’s National Medical Center

GBM:

Glioblastoma multiforme

BSG:

Brain stem glioma

LDH:

Lactate dehydrogenase

PD:

Progressive disease

SD:

Stable disease

PR:

Partial response

CR:

Complete response

bFGF:

Basic fibroblastic growth factor

PDGF:

Platelet derived growth factor

VEGF:

Vascular endothelial growth factor

S.T.E.P.S.® :

System for Thalidomide Education and Prescribing Safety

FDG PET:

18-Fluorodeoxyglucose positron emission tomography

TTP:

Time to progression

TTD:

Time to death

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Acknowledgements

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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Authors and Affiliations

  1. Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, SW 331, Boston, MA, 02115, USA

    Christopher D. Turner, Susan Chi, Caitlin Briody, Christine Chordas, Mary Ann Zimmerman & Mark W. Kieran

  2. Department of Medicine, Division of Radiation Oncology, Children’s Hospital Boston, Boston, MA, USA

    Karen J. Marcus

  3. Departments of Neurology and Hematology/Oncology, Children’s National Medical Center, Washington, DC, USA

    Tobey MacDonald & Roger J. Packer

  4. Department of Radiology, Children’s Hospital Boston, Boston, MA, USA

    Tina Young Poussaint & Sridhar Vajapeyam

  5. Department of Neurology, Children’s Hospital Boston, Boston, MA, USA

    Nicole Ullrich

  6. Department of Neurosurgery, Children’s Hospital Boston, Boston, MA, USA

    Liliana C. Goumnerova & R. Michael Scott

Authors
  1. Christopher D. Turner
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  2. Susan Chi
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  3. Karen J. Marcus
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  4. Tobey MacDonald
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  5. Roger J. Packer
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  6. Tina Young Poussaint
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  7. Sridhar Vajapeyam
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  8. Nicole Ullrich
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  9. Liliana C. Goumnerova
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  10. R. Michael Scott
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  11. Caitlin Briody
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  12. Christine Chordas
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  13. Mary Ann Zimmerman
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  14. Mark W. Kieran
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Corresponding author

Correspondence to Christopher D. Turner.

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Turner, C.D., Chi, S., Marcus, K.J. et al. Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme. J Neurooncol 82, 95–101 (2007). https://doi.org/10.1007/s11060-006-9251-9

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  • DOI: https://doi.org/10.1007/s11060-006-9251-9

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