Easier way to approach question. Look at the creatinine value it is elevated, Methotrexate is renally excreted so we can preview an increase in levels due to impaired renal excretion which leads to chemotoxicity. Leucovorin is a common chemoprotectant used to avoid Metotrexate toxicities.
Why do you give IV leucovorin with intrathecal methotrexate? Wouldnโt MTX lose its efficacy since leucovorin reverses the effects of MTX?
I just wanted to add a note here. I was confused on why you would give the patient leucovorin with the MTX. The reason is that it "rescues" the normal cells from damage/death, and allows the MTX to attack only the cancer cells.
Also another connection we may need to know is that if leucovorin with 5-FU it makes it more effective/toxic at killing cancer cells!
submitted by โsajaqua1(607)
This answer rests on the difference between Folate and Leucovorin. Intrathecal methotrexate is given to block dihydrofolate reductase (DHFR) from making folic acid into DHF, and then turning that DHF into THF. This is done to prevent the production of downstreamn products necessary for metabolism including DNA synthesis. Leucovorin (also called 5-formy-lTHF) can be used to sidestep this product by being put into play downstream. See the diagram here: https://www.emed.com.au/folic-acid-and-fertility-doing-more-harm-than-good/ Folate is listed as Folic Acid, methotrexate interferes with DHFR, and Leucovorin is 5-formyl-THF. There is also further description here: https://www.drugbank.ca/drugs/DB00158
Why does this not simply undo the action of methotrexate? This is because many cancers do not have the reduced folate carrier. So the cancers pick up folate and methotrexate, and their DNA synthesis is reduced. Meanwhile other healthy cells can pick up the Leucovorin and stave off some of the worst effects. Remember, leucovorin cannot be given intrathecally.
https://www.d.umn.edu/~jfitzake/Lectures/DMED/Antineoplastics/DNASynthesisInhibitors/Methotrexate/LeucovorinRescue.html