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**Doxorubicin + cisplatin + methotrexate + ifosfamide** is a four-drug chemotherapy combination regimen primarily used in the treatment of osteosarcoma, a highly malignant bone tumor more common in children and young adults. This regimen, often referred to as "MDCI" or "MAPI" (methotrexate, doxorubicin, cisplatin, ifosfamide), is considered the mainstay of multi-agent chemotherapy protocols for this condition. - **Doxorubicin** is an anthracycline antibiotic that inhibits topoisomerase II, leading to DNA damage and apoptosis. - **Cisplatin** is a platinum-based compound that forms DNA crosslinks, inhibiting DNA replication and transcription, resulting in tumor cell death. - **Methotrexate** is an antimetabolite that inhibits dihydrofolate reductase, blocking DNA synthesis, repair, and cellular replication. - **Ifosfamide** is an alkylating agent that induces crosslinking of DNA strands, interfering with the growth of cancer cells. This combination is effective but associated with significant toxicities, including myelosuppression, nephrotoxicity, neurotoxicity, mucositis, gastrointestinal toxicity, and possible cardiotoxicity (from doxorubicin) and ototoxicity (from cisplatin). The combination aims to maximize cancer cell kill and reduce drug resistance by using agents with different mechanisms of action. This protocol is supported by major guidelines such as the NCCN and is standard of care in many healthcare systems for localized and nonmetastatic osteosarcoma[1][3][5][9].
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