A phase 1 study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors.

ABSTRACT:

Background

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can inhibit tumor proliferation, angiogenesis, and restore apoptosis in preclinical pediatric solid tumor models. We conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of simvastatin with topotecan and cyclophosphamide in children with relapsed/refractory solid and central nervous system (CNS) tumors.

Methods

Simvastatin was administered orally twice daily on days 1-21, with topotecan and cyclophosphamide intravenously on days 1-5 of a 21-day cycle. Four simvastatin dose levels (DLs) were planned, 140 (DL1), 180 (DL2), 225 (DL3), 290 (DL4) mg/m² /dose, with a de-escalation DL of 100 mg/m² /dose (DL0) if needed. Pharmacokinetic and pharmacodynam

SUBMITTER: Cash T 

PROVIDER: S-EPMC11225565 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature