5-fluorouracil + leucovorin + phosphonacetyl-L-aspartic acid

The combination of 5-fluorouracil (5-FU), leucovorin (LV), and phosphonacetyl-L-aspartic acid (PALA) is a chemotherapy regimen that has been studied primarily for advanced malignancies, particularly colorectal cancer. This combination works through biochemical modulation, where PALA and leucovorin enhance the cytotoxic effects of 5-FU. ## Mechanism of Action This combination therapy works through multiple mechanisms: 1. **5-Fluorouracil (5-FU)**: A pyrimidine analog that inhibits thymidylate synthase (TS), preventing DNA synthesis and repair in rapidly dividing cells. 2. **Leucovorin (LV)**: A 5-formyl derivative of tetrahydrofolate that increases the intracellular folate pool, particularly 5,10-methylene-THF, which enhances 5-FU's binding to thymidylate synthase. 3. **Phosphonacetyl-L-aspartic acid (PALA)**: Administered as a biochemical modulator that enhances 5-FU activity by inhibiting pyrimidine synthesis.