DIPG/DIPT Discussion

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A searchable blog on DIPG research, DIPG news, recent publications, DIPG Foundations, DIPG researchers, clinical trials as well as other issues relating to Diffuse Intrinsic Pontine Tumors- both Diffuse Intrinsic Pontine Gliomas (DIPGs) and Atypical Pontine Lesions (APLs).

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Friday, December 9, 2011

A phase 2 study of pegylated interferon α-2b (PEG-Intron®) in children with diffuse intrinsic pontine glioma

The NIH based study lead by Kathy Warren utilizing low dose pegylated interferon for children with newly diagnosed DIPGs recently was published on line ahead of print in the journal Cancer.  The rationale behind this study was the finding that low dose administration of interferon alfa produced” more significant inhibition of angiogenesis-regulating genes, tumor vascularization, and tumor growth compared with the higher intermittent dose schedule. These effects were lost at higher doses, suggesting that metronomic administration of IFNs may have a more robust antitumor effect.”

In this study, 32 children between the ages of 1.8 and  14.8 years (mean 5.3 years) were given pegylated interferon subcutaneously (a shot under the skin) weekly starting 2-10 weeks after radiation until disease progression or unacceptable toxicity.  The idea was to try to have a continuous low dose of inferferon.

There were no grade 4 toxicities and no child stopped interferon because of toxicity.

The overall survival at 2 years was 14.3%  The median time to progression from diagnosis was 235 days, and the median OS from diagnosis was 351 days. 

The authors concluded, “Although low-dose PEG-Intron therapy did not significantly improve 2-year survival in children with DIPG compared with an historic control population, it did delay the time to progression.”

The narrowness of the eligibility criteria in this study is particularly interesting as it shows the advancement in understanding that not all brainstem tumors are the same.   This stricter eligibility criterion seems to be trying to eliminate those tumors that might have an underlying aspect giving it a better prognosis and thus skew the data.  The eligibility criteria defined as:
  • Age less than 21 years
  • Diffuse intrinsic tumor with epicenter presumed in the pons
  • Signal abnormality involving 50% or more of the pons on T2-weighed sequence at diagnosis
  • Involvement of the ventral pons
  • No expophytic component
  • No patients with known or suspected neurofibromatosis type 1

The paper pointed out that the increasing delineation of a DIPG tumor can make it very difficult to compare results with past papers that did not define the patient population in this way.   Those that previously included focal tumors and those with exophytic components might have mistakenly high overall survival statistics.  For those interested in comparing studies analysis of the eligibility criteria is going to be important.

A phase 2 study of pegylated interferon α-2b (PEG-Intron®) in children with diffuse intrinsic pontine glioma Cancer.  2011 Nov 15. doi: 10.1002/cncr.26659. [Epub ahead of print]