methotrexate + etoposide + hydroxyurea + teniposide

This combination therapy consists of four antineoplastic agents: methotrexate, etoposide, hydroxyurea, and teniposide. Each drug has distinct mechanisms of action: - **Methotrexate** is an antimetabolite that inhibits dihydrofolate reductase, thereby blocking DNA synthesis and cell division[4]. - **Etoposide** is a topoisomerase II inhibitor, preventing DNA strand rejoining and resulting in DNA strand breaks[6]. - **Hydroxyurea** is a ribonucleotide reductase inhibitor, reducing the production of DNA building blocks and halting cell cycle progression in the S phase[7]. - **Teniposide** is another topoisomerase II inhibitor with high liposolubility, allowing it to cross the blood-brain barrier and exhibit prolonged activity[1]. This combination is used for its potential synergistic effects in aggressive malignancies, especially where blood-brain barrier penetration is required. There is limited clinical data on this exact combination, but individual components or related combinations (e.g., methotrexate + teniposide) have been investigated in hematologic malignancies and primary CNS lymphoma[1][3]. The rationale for such combinations is to target multiple phases of the cell cycle and different molecular pathways to improve cytotoxic effect and overcome resistance.