leucovorin
Meaning of leucovorin: The same molecule rescues healthy tissue from one chemotherapy drug and sharpens the action of another, depending on which it is paired with.
Definition of leucovorin
Leucovorin is a reduced, ready-to-use form of folate, the vitamin cells need in order to build DNA. Because it is already in the active form, it bypasses the enzyme that methotrexate blocks. Given on a strict schedule after high-dose methotrexate, it restores folate to normal tissue. Paired with fluorouracil instead, it does the opposite and strengthens that drug's effect.
How does leucovorin rescue work?
Methotrexate blocks the enzyme that converts folate into its usable form. Without usable folate, no cell can build the components of DNA, and the cells hit hardest are the ones dividing fastest: the bone marrow and the lining of the mouth and gut alongside the tumor. Leucovorin arrives already reduced, so it does not need the blocked enzyme at all and refills the folate pool directly. Timing decides everything. Started too early, it protects the cancer as well as the healthy tissue; started too late, the damage is already done. Doses are therefore given at set intervals after the methotrexate infusion and continued until blood levels of methotrexate have fallen far enough.
Why does it strengthen fluorouracil?
| With methotrexate | With fluorouracil | |
|---|---|---|
| Purpose | Protect normal cells | Increase the drug's effect on the tumor |
| How | Restores active folate the drug removed | Supplies the folate that locks the drug onto its target enzyme |
| When given | Hours after the chemotherapy | Alongside it in the same regimen |
The fluorouracil combination is a backbone of treatment for colorectal cancer. The two roles look contradictory but follow from the same chemistry, since one drug removes active folate and the other needs it present.
What else is it used for?
Leucovorin treats megaloblastic anemia caused by folate deficiency where an oral vitamin is not suitable. It counteracts other folate-blocking drugs such as pyrimethamine and trimetrexate, and it is the treatment for accidental methotrexate overdose. It is not the same substance as folic acid, which still needs enzymatic conversion and therefore cannot perform the rescue. A refined version containing only the active mirror-image form of the molecule, levoleucovorin, is used in the same settings at a proportionally lower dose.
Also known as
Used in a sentence
Leucovorin was administered on a timed schedule following the high-dose methotrexate infusion.
Good to know
Leucovorin rescue refers specifically to its timed use after high-dose methotrexate, which is a different purpose from its use alongside fluorouracil, where it increases rather than counteracts the effect of the chemotherapy.