High-dose methotrexate with calcium leucovorin rescue forms part of standard osteosarcoma chemotherapy. The rescue is given because leucovorin:

• A Enhances methotrexate uptake into tumour cells
• B Bypasses dihydrofolate reductase inhibition in normal cells ✓
• C Accelerates renal excretion of methotrexate
• D Neutralises circulating methotrexate by direct binding

Explanation

Methotrexate kills cells by inhibiting dihydrofolate reductase, depleting reduced folates needed for thymidylate and purine synthesis. Leucovorin is reduced folate (5-formyl tetrahydrofolate) that enters normal cells and restores nucleotide synthesis without requiring DHFR, thereby rescuing normal marrow and mucosa. It does not bind methotrexate or enhance its excretion, though hydration and urine alkalinisation are used separately to speed renal clearance. Tumour rescue is incomplete because of impaired transport.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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