A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG)

Autor: Mariko, DeWire, Christine, Fuller, Trent R, Hummel, Lionel M L, Chow, Ralph, Salloum, Peter, de Blank, Luke, Pater, Sarah, Lawson, Xiaoting, Zhu, Phil, Dexheimer, Adam C, Carle, Shiva Senthil, Kumar, Rachid, Drissi, Charles B, Stevenson, Adam, Lane, John, Breneman, David, Witte, Blaise V, Jones, James L, Leach, Maryam, Fouladi
Rok vydání: 2020
Předmět:
Zdroj: Journal of neuro-oncology. 149(3)
ISSN: 1573-7373
Popis: Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients.Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/mThe study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ .Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies.NCT02607124.
Databáze: OpenAIRE
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