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methotrexate + etoposide + dexamethasone + pegaspargase
- Development stage
- Phase 2
- Lead developer
- Pfizer
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Therapeutic Enzymes → Recombinant Proteins and Enzymes
- Administration
- Intravenous, Intramuscular, Oral
01
Overview
This is a four-drug chemotherapy combination consisting of methotrexate (an antimetabolite and antifolate agent), etoposide (a topoisomerase II inhibitor), dexamethasone (a synthetic glucocorticoid corticosteroid), and pegaspargase (a pegylated form of L-asparaginase). The regimen is primarily used for the treatment of advanced or relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENK/TCL). Methotrexate inhibits dihydrofolate reductase to block DNA synthesis. Etoposide induces DNA strand breaks by inhibiting topoisomerase II. Dexamethasone exerts anti-inflammatory and immunosuppressive effects via glucocorticoid receptor agonism. Pegaspargase depletes asparagine by catalyzing its hydrolysis to aspartic acid and ammonia, starving tumor cells that cannot synthesize asparagine. This combination has demonstrated high response rates in ENK/TCL with manageable toxicity profiles[1][6][7][8].
- Other names
- methotrexate, etoposide, dexamethasone, and pegaspargase combinationMEDA regimenMESA regimen
02
Targets
DHFR (Dihydrofolate reductase)GR (Glucocorticoid receptor)TOP2A (DNA topoisomerase II)
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