• Jack M Su, Patrick Thompson, Adekunle Adesina, Xiao-Nan Li, Lindsay Kilburn, Arzu Onar-Thomas, Mehmet Kocak, Brenda Chyla, Evelyn McKeegan, Katherine E Warren, Stewart Goldman, Ian F Pollack, Maryam Fouladi, Alice Chen, Vincent Giranda, James Boyett, Larry Kun, and Susan M Blaney.
• Texas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
• Neuro-oncology. 2014 Dec 1; 16 (12): 1661-8.

BackgroundA phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic parameters and extent of PARP inhibition in peripheral blood mononuclear cells (PBMCs) following veliparib.MethodsTMZ was given once daily and veliparib twice daily for 5 days every 28 days. Veliparib concentrations and poly(ADP-ribose) (PAR) levels in PBMCs were measured on days 1 and 4. Analysis of pharmacokinetic and PBMC PAR levels were performed twice during study conduct to rationally guide dose modifications and to determine biologically optimal MTD/RP2D.ResultsTwenty-nine evaluable patients were enrolled. Myelosuppression (grade 4 neutropenia and thrombocytopenia) were dose limiting. The RP2Ds are veliparib 25 mg/m(2) b.i.d. and TMZ 135 mg/m(2)/d. Only 2 out of 12 patients treated at RP2Ds experienced dose-limiting toxicities. Although no objective response was observed, 4 patients had stable disease >6 months in duration, including 1 with glioblastoma multiforme and 1 with ependymoma. At the RP2D of veliparib, pediatric pharmacokinetic parameters were similar to those in adults.ConclusionsVeliparib and TMZ at the RP2D were well tolerated in children with recurrent brain tumors. A phase I/II trial to evaluate the tolerability and efficacy of veliparib, TMZ, and radiation in children with newly diagnosed brainstem gliomas is in progress.© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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