First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma.

ABSTRACT:

Purpose

Standard treatment for glioblastoma (GBM) includes surgery, radiation therapy (RT), and temozolomide (TMZ), yielding a median overall survival (OS) of approximately 14 months. Preclinical models suggest that pharmacologic ascorbate (P-AscH^-) enhances RT/TMZ antitumor effect in GBM. We evaluated the safety of adding P-AscH^- to standard RT/TMZ therapy.

Patients and methods

This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH^-) and an adjuvant (ADJ) phase (post RT/TMZ/P-AscH^- phase). Eight P-AscH^- dose cohorts were evaluated in the RT phase until targeted plasma ascorbate levels were achieved (≥20 mmol/L). In the ADJ phase, P-AscH^- doses were escalated in each subject at each c

SUBMITTER: Allen BG 

PROVIDER: S-EPMC6858950 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature