A 16-year-old boy with osteosarcoma receives high-dose methotrexate infusion followed by leucovorin rescue started 24 hours later. The purpose of this timed rescue is to:
- A Enhance methotrexate entry into tumor cells
- B Provide reduced folates to normal cells once methotrexate has cleared from them ✓
- C Accelerate renal excretion of unchanged methotrexate
- D Prevent the mucositis caused by methotrexate metabolites in the colon
Correct answer: B. Provide reduced folates to normal cells once methotrexate has cleared from them
Explanation
Leucovorin is N5-formyl tetrahydrofolate, a fully reduced folate that bypasses dihydrofolate reductase entirely. Because high-dose methotrexate saturates transport into resistant tumor cells but clears rapidly from normal marrow and mucosa, giving leucovorin about 24 hours later restores folate pools selectively in host tissues while sparing the antitumor effect. It does not alter methotrexate excretion, and glucarpidase rather than leucovorin is used when elimination is severely impaired.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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