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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.

ABSTRACT: BACKGROUND:We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). PATIENTS AND METHODS:Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, ? = 0.10. RESULTS:Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. CONCLUSION:Capecitabine did not improve the outcome for children with newly diagnosed DIPG.

SUBMITTER: Kilburn LB

PROVIDER: S-EPMC5774861 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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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.

Kilburn Lindsay B LB Kocak Mehmet M Baxter Patricia P Poussaint Tina Young TY Paulino Arnold C AC McIntyre Christine C Lemenuel-Diot Annabelle A Lopez-Diaz Christine C Kun Larry L Chintagumpala Murali M Su Jack M JM Broniscer Alberto A Baker Justin N JN Hwang Eugene I EI Fouladi Maryam M Boyett James M JM Blaney Susan M SM

Pediatric blood & cancer 20171101 2

<h4>Background</h4>We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG).<h4>Patients and methods</h4>Children 3-17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m<sup>2</sup> /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks st ...[more]

PMID: 29090526

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Project description:OBJECT:Coinfused surrogate imaging tracers can provide direct insight into the properties of convection-enhanced delivery (CED) in the nervous system. To better understand the distributive properties of CED in a clinical circumstance, the authors analyzed the imaging findings in pediatric diffuse intrinsic pontine glioma (DIPG) patients undergoing coinfusion of Gd-DTPA and interleukin-13-Pseudomonas exotoxin (IL13-PE). METHODS:Consecutive patients undergoing CED (maximal rates of 5 or 10 ?l/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 ?g/ml or 0.25 ?g/ml) for DIPG were included. Real-time MRI was performed during infusions, and imaging results were analyzed. RESULTS:Four patients (2 males, 2 females; mean age at initial infusion 13.0 ± 5.3 years; range 5-17 years) underwent 5 infusions into DIPGs. Brainstem infusions were clearly identified on T1-weighted MR images at 1-mM (1 infusion) and 5-mM (4 infusions) coinfused Gd-DTPA concentrations. While the volume of distribution (Vd) increased progressively with volume of infusion (Vi) (mean volume 2.5 ± 0.9 ml; range 1.1-3.7 ml), final Vd:Vi ratios were significantly reduced with lower Gd-DTPA concentration (Vd:Vi for 1 mM of 1.6 compared with a mean Vd:Vi ratio for 5 mM of 3.3 ± 1.0) (p = 0.04). Similarly, anatomical distribution patterns were affected by preferential flow along parallel axial fiber tracts, into prior infusion cannula tracts and intraparenchymal air pockets, and leak back around the infusion cannula at the highest rate of infusion. CONCLUSIONS:Magnetic resonance imaging of a coinfused Gd-DTPA surrogate tracer provided direct insight into the properties of CED in a clinical application. While clinically relevant Vds can be achieved by convective delivery, specific tissue properties can affect distribution volume and pattern, including Gd-DTPA concentration, preferential flow patterns, and infusion rate. Understanding of these properties of CED can enhance its clinical application. Part of clinical trial no. NCT00880061 ( ClinicalTrials.gov ).

Dataset Information

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.

Publications

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.

Similar Datasets

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