A phase I trial of metformin in combination with vincristine, irinotecan, and temozolomide in children with relapsed or refractory solid and central nervous system tumors: A report from the national pediatric cancer foundation.

ABSTRACT:

Background

Patients with relapsed and refractory solid and central nervous system (CNS) tumors have poor outcomes and need novel therapeutic options. Vincristine, irinotecan, and temozolomide (VIT) is a common chemotherapy regimen in relapsed pediatric tumors with an established toxicity profile. Metformin shows preclinical anti-cancer activity through multiple pathways.

Methods

The objective of this Phase I trial was to establish the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of metformin in combination with VIT in children with relapsed and refractory solid and CNS tumors. A 3 + 3 design was used to test the addition of metformin at five dose levels (666, 999, 1333, 1666, and 2000 mg/m² /day). Therapy toxicity, pharmacokinetics, and radiol

SUBMITTER: Metts JL 

PROVIDER: S-EPMC9972017 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature