Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Aug;68(8):e29031.
doi: 10.1002/pbc.29031. Epub 2021 Apr 12.

Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: Report of a COG randomized Phase II screening trial

Adam S Levy  1 , Mark Krailo  2 , Susan Chi  3 , Doojduen Villaluna  4 , Linda Springer  4 , Chris Williams-Hughes  2 , Maryam Fouladi  5 , Amar Gajjar  6
Affiliations
Clinical Trial

Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: Report of a COG randomized Phase II screening trial

Adam S Levy et al. Pediatr Blood Cancer. 2021 Aug.

Abstract

Background: Approximately 30% of children with medulloblastoma (MB) experience recurrence, which is usually incurable. This study compared the overall survival (OS) of patients receiving temozolomide (TMZ) and irinotecan with that of patients receiving TMZ, irinotecan, and bevacizumab for recurrent MB/central nervous system (CNS) primitive neuroectodermal tumor (PNET).

Methods: Patients with relapsed/refractory MB or CNS PNET were randomly assigned to receive TMZ (150 mg/m2 /day PO on days 1-5) and irinotecan (50 mg/m2 /day IV on days 1-5) with or without bevacizumab (10 mg/kg IV on days 1 and 15).

Results: One hundred five patients were eligible and treated on study. Median OS was 13 months in the standard arm and 19 months with the addition of bevacizumab; median event-free survival (EFS) was 6 months in the standard arm and 9 months with the addition of bevacizumab. The hazard ratio for death from the stratified relative-risk regression model is 0.63. Overall, 23 patients completed 12 courses of planned protocol therapy, 23% (12/52) in the experimental arm with bevacizumab versus 21% (11/53) in the standard arm. Toxicity profiles were comparable in both treatment arms. The estimate of the incidence of feasibility events associated with the bevacizumab arm is three of 52 (5.8%) (95% CI 1.2-16%). Events included myelosuppression, electrolyte abnormalities, diarrhea, and elevated transaminases. One intracranial hemorrhage event was observed in each arm.

Conclusion: The addition of bevacizumab to TMZ/irinotecan significantly reduced the risk of death in children with recurrent MB. The combination was relatively well tolerated in this heavily pretreated cohort. The three-drug regimen demonstrated a sufficient risk reduction to warrant further investigation.

Keywords: PNET; bevacizumab; irinotecan; recurrent medulloblastoma; temozolomide.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: None

Figures

FIGURE 1.
FIGURE 1.
Study participation and flow through the trial.
FIGURE 2.
FIGURE 2.
Overall Survival and Event Free Survival for all enrolled patients (figures on the left) and Overall Survival and Event Free Survival for all medulloblastoma patients (figures on the right).
FIGURE 3.
FIGURE 3.
Overall Survival of Medulloblastoma patients for which molecular classification was available.
See this image and copyright information in PMC

References

    1. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D6, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016. Jun;131(6):803–20. doi: 10.1007/s00401-016-1545-1. Epub 2016 May 9. DOI:10.1007/s00401-016-1545-1 - DOI - DOI - PubMed
    1. Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, Kool M7, Dufour C, Vassal G, Milde T, Witt O, von Hoff K, Pietsch T, Northcott PA 13, Gajjar A, Robinson GW, Padovani L, André N, Massimino M, Pizer B, Packer R, Rutkowski S, Pfister SM, Taylor MD, Pomeroy SL. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol. 2016. Jun;131(6):821–31. doi: 10.1007/s00401-016-1569-6. Epub 2016 Apr 4.. DOI: 10.1007/s00401-016-1569-6. - DOI - DOI - PMC - PubMed
    1. Ramaswamy V, Taylor MD. Medulloblastoma: From Myth to Molecular. J Clin Oncol. 2017. Jul 20;35(21):2355–2363. doi: 10.1200/JCO.2017.72.7842. Epub 2017 Jun 22..DOI: 10.1200/JCO.2017.72.7842 - DOI - DOI - PubMed
    1. Gajjar A, Bowers DC, Karajannis MA, Leary S, Witt H, Gottardo NG. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape. J Clin Oncol. 2015. Sep 20;33(27):2986–98. doi: 10.1200/JCO.2014.59.9217. Epub 2015 Aug 24. DOI: 10.1200/JCO.2014.59.9217 - DOI - DOI - PMC - PubMed
    1. Gururangan S, Krauser J, Watral MA, et al. Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma. Neuro-Oncology. 2008;10(5):745–751. doi:10.1215/15228517-2008-044. - DOI - PMC - PubMed

Publication types

MeSH terms