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metformin + vincristine + dexamethasone + doxorubicin + pegaspargase
- Development stage
- Unknown
- Lead developer
- Moffitt Cancer Center
- Modality
- Recombinant Proteins and Enzymes, Small Molecules
- Administration
- Oral, Intravenous, Intramuscular, Intrathecal
01
Overview
This investigational combination chemotherapy regimen, developed by the H. Lee Moffitt Cancer Center and Research Institute, consists of metformin added to a VPLD backbone (vincristine, dexamethasone, doxorubicin, and pegaspargase) for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children and young adults. Metformin, traditionally an oral anti-diabetic medication, is utilized here for its ability to activate AMP-activated protein kinase (AMPK), which subsequently inhibits the unfolded protein response and induces endoplasmic reticulum stress in leukemia cells. The VPLD components provide standard cytotoxic effects through microtubule inhibition, glucocorticoid receptor activation, DNA intercalation, and asparagine depletion. A Phase I dose-escalation trial (NCT01324180) evaluated the safety and maximum tolerated dose of this combination, demonstrating it to be tolerable in heavily pretreated patients.
- Other names
- Metformin + VPLDMetformin with VPLD ChemotherapyMetformin with Induction Chemotherapy of Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase
02
Targets
ND1 (Mitochondrial electron transport chain complex I)AMPK (Adenosine monophosphate–activated protein kinase)TUBB (Tubulin (alpha and beta subunits))TOP2A (DNA topoisomerase II)DNAGR (Glucocorticoid receptor)
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