In:
Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-09-29)
Abstract:
Purpose: Pharmacological ascorbate (P-AscH-) is hypothesized to be an Fe-dependent tumor-specific adjuvant to chemo-radiation in treating glioblastoma (GBM). The current study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase 2 clinical trial while simultaneously investigating a mechanism-based, non-invasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. Patients and Methods: The single-arm phase 2 clinical trial (NCT02344355) enrolled 55 subjects with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. 49 of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. Results: Median OS was estimated to be 19.6 months (90% CI: 15.7 – 26.5 months), a statistically significant increase compared to historic control patients (14.6 months). Subjects with initial T2* relaxation & lt; 50 ms were associated with a significant increase in PFS compared to T2*high subjects (11.2 months vs. 5.7 months, p & lt;0.05) and a trend towards increased OS (26.5 months vs. 17.5 months). These results were validated in pre-clinical in vitro and in vivo model systems. Conclusions: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-22-3952
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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