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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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Wednesday, April 24, 2013

Capecitabine Phase 1 Trial Publication

As a dose-escalating phase 1, this trial's main objective was to establish the maximum tolerated dose and toxicity of capecitabine (Xeloda) in a pediatric population (between the ages of 3 and 21).   The drug was given for nine weeks in two daily doses from the start of radiation.   There was then a two week break followed by another 3 cycles of capecitabine in which the drug was given twice daily for two weeks followed by a one week break.

From a parent perspective, a very cool thing about capecitabine is that this flavored, film coated, rapidly disintegrating tablet did not have to be swallowed intact but could be disolved in water.   There have been other studies where the younger patients were excluded because of the inability to swallow pills intact.

The way capecitabine works is that it is a pro-drug and can be broken down to 5-fluorouracil (5-FU) by a cellular enzyme thymidine phosphorylase (TP).  TP is found at significantly higher levels in many cancers.   Only 5-FU has antiproliferative properties.   The hope is that then the active metabolite 5FU will concentrate specifically in the tumor cells.  In addition, radiation induces the enzyme TP.   

5 FU has been around as a antimetabolite chemotherapy on its own since it was patented in the late 1950's.  The way it works is that 5 FU blocks an enzyme (thymidylate synthase inhibitor) which allows the cell to make a protein that is needed for DNA.   Without this, cells can not make new DNA needed for cell division and thus undergo a "thymineless death".

Since TP has been found in increased level in gliomas, it was thought that a combination of capecitabine and radiation could be a way to attack pediatric DIPGs and high grade gliomas.    Of note, capecitabine has been effective for breast cancer brain metastases.

Of the 24 enrolled kids, 15 patients had DIPG.  The dose-limiting toxicity included grade 2 and 3 palmar/plantar erythroderma and grade 2 and elevation of a liver enzyme alanine aminotransferase.

This trial (PBTC-021) was run from at the institutions of the Pediatric Brain Tumor Consortium. Interestingly, the phase 2 (PBTC-30) has also finished patient accural.   .  Although the hope of radiosensitizers in general for DIPG have not lived up to expections, this radiosensitzer seems to have other effects which perhaps might have increased effectiveness.   The phase 2 is expected to complete data collection in June 2013.   Hopefully,  meeting abstracts or publication will follow shortly thereafter.

Phase I trial of capecitabine rapidly disintegrating tablets and con concomitant radiation therapy in children with newly diagnosed brainstem glioma and high-grade gliomas

Capecitabine therapy of central nervous system metastases from breast cancer

Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report

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