A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas
Outcome for children with diffuse intrinsic pontine gliomas (DIPG) remains dismal. Radiation has been shown to increase the pharmacodynamic effect of capecitabine. The primary aim of this study was to estimate PFS for children with DIPG treated with combination of capecitabine and RT.
Children 3-17 years of age with newly diagnosed DIPG without prior experimental treatment. Histology was not required. Capecitabine was initiated within 24 hr of the initiation of RT and was administered over 20 weeks. Conventional or conformal RT was administered to all patients once daily 5 days a week in 180 cGy/day fractions to a total dose of 5,580 cGy.
Thirty-five children with DIPG, all eligible, were enrolled from February 2010 to May 2011 and combines with data from 10 patients from a phase 1 study. 25 patients completed the planned protocol. 3 withdrew from treatment. Therapy was well tolerated. There was earlier progression with the capecitabine group, with 6 and 12-month PFS of 33.7% and 7.2% compared to 54.7% and 15.6% in the historical control, respectively. There was no difference in OS. Shorter PFS hypothesized to be pseudoprogression in response to therapy.
Non-randomized study, so reason for shorter PFS is unclear. Regardless, this study design remains the standard for evaluating new agents in children with DIPG since the outcomes in children with DIPG have not changed over time.