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

Abstract

Capecitabine with concurrent RT was generally well tolerated. The recommended phase II capecitabine dose when given with concurrent RT is 650 mg/m(2), administered twice daily. A phase II study to evaluate the efficacy of this regimen in children with intrinsic brainstem gliomas is in progress (PBTC-030).

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

“…Initial patients were assigned to schedules A and B, which were utilized in the phase I study. 18 Subsequently the sampling was further reduced to encourage participation and in schedule C samples were obtained on days 1 and 14 at predose, and 0.5, 1, 3 and 6 hours after dosing as well as 1–4 hours after the morning dose on days 7 and 21. Determination of plasma concentrations of capecitabine and its metabolites (5′-deoxy-5-fluorocytidine [DFCR], 5′-deoxy-5-fluorouridine [DFUR], 5-FU, and α-fluoro-β-alanine [FBAL]) was done using a validated liquid chromatography (LC) method with mass spectrometry detection.…”

“…Determination of plasma concentrations of capecitabine and its metabolites (5′-deoxy-5-fluorocytidine [DFCR], 5′-deoxy-5-fluorouridine [DFUR], 5-FU, and α-fluoro-β-alanine [FBAL]) was done using a validated liquid chromatography (LC) method with mass spectrometry detection. 18 Pharmacokinetic parameters (C max , t max , AUC 6h and t 1/2 ) of capecitabine and its metabolites were estimated individually on days 1 and 14 of the RT phase using non-compartmental methods using WinNonlin version 6.2 software.…”

“…17 A prior Pediatric Brain Tumor Consortium (PBTC) trial demonstrated that the recommended phase II capecitabine dose during radiotherapy for children with newly diagnosed high-grade or brainstem gliomas was 650 mg/m 2 /dose administered twice daily. [ 18 ] Single agent capecitabine, 1250 mg/m 2 /dose, administered twice daily for 14 consecutive days of a 21-day course, was administered post radiotherapy for 3 courses. Of note, a new rapidly disintegrating tablet (RDT) formulation was created for the phase I and II trials to facilitate enrollment of children unable to swallow pills.…”

“…Preliminary pharmacokinetic data from the phase I trial demonstrated that the disposition of the RDT in children was similar to that of adults receiving the standard capecitabine formulation. 18 …”

“…Of note, a new rapidly disintegrating tablet (RDT) formulation was created for the phase I and II trials to facilitate enrollment of children unable to swallow pills. Preliminary pharmacokinetic (PK) data from the phase I trial demonstrated that the disposition of the RDT in children was similar to that of adults receiving the standard capecitabine formulation …”