LEUCOVORIN RESCUE
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administration of LEUCOVORIN along with high dose METHOTREXATE rescues host tissues from the effects of the intense MTX therapy
- LEUCOVORIN (= folinic acid, a reduced form of folate) provides the normal tissues with a mechanism to bypass normal tetrahydrofolate synthesis pathways, which circumvents the inhibition of DHFR (selective toxicity)
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relies on the fact that some cancer cells do not express a functional reduced folate carrier, and cannot take up LEUCOVORIN
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- net result is that you can use higher dose of MTX
- more antitumor action without increasing toxicity
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decreased resistance - higher dose can convert resistant cells into susceptible cells (if mechanism of resistance involves inability to actively transport MTX into cell, higher doses result in higher extracellular concentrations which promote diffusion and uptake via the folate receptor)
- LEUCOVORIN cannot be given intrathecally à fatal