MAP is the standard chemotherapy regimen for high-grade osteosarcoma, combining high-dose methotrexate, doxorubicin (Adriamycin), and cisplatin. It forms the backbone of pre- and post-operative (perioperative) chemotherapy for resectable osteosarcoma.
High-grade, resectable, non-metastatic osteosarcoma — pre-operative (neoadjuvant) and post-operative (adjuvant) chemotherapy.
MAP (perioperative, every 3 weeks):
Pre-op cycles 1–2: High-dose methotrexate 12 g/m² IV over 4 hours (with leucovorin rescue), doxorubicin 75 mg/m² IV, cisplatin 100–120 mg/m² IV.
Post-op cycles: Continue MAP for additional cycles based on histologic response. Leucovorin rescue mandatory after high-dose MTX. Monitor methotrexate levels. Aggressive hydration with cisplatin cycles.
Myelosuppression (90%), Nausea/Vomiting (80%), Mucositis (50%), Alopecia (85%), Cardiotoxicity (10%), Nephrotoxicity (20%), Ototoxicity (30%), Fatigue (75%)
Adverse reaction frequencies reflect combination regimen data. Consult individual prescribing information for complete details.
MAP achieves cytotoxicity through three distinct mechanisms: High-dose Methotrexate inhibits dihydrofolate reductase (DHFR), depleting tetrahydrofolate required for purine and thymidylate synthesis. Doxorubicin intercalates into DNA, inhibits topoisomerase II, and generates free radicals. Cisplatin forms intrastrand and interstrand DNA cross-links. Leucovorin rescue after MTX rescues normal tissues while tumor cells (deficient in leucovorin transport) die.