Currently, a doxorubicin-based regimen should be considered standard therapy for patients with advanced, unresectable STS. Unfortunately, treatment is limited by cardiomyopathy, which occurs in about 10% of patients, and can result in death. Cardiac toxicity can be diminished by giving the drug as a continuous infusion as opposed to a bolus, without comprising therapeutic efficacy. Ifosfamide is the most promising recent addition to the chemotherapeutic armamentarium for patients with stage IV disease. Ifosfamide is a cyclophosphamide analogue that is activated by hepatic microsomes. When used in combination with doxorubicin, response of 30-35% can be achieved.18 Hemorrhagic cystitis, the major toxicity of ifosfamide, can be prevented by use of the uroprotectant agent, mesna. Myelosuppression occurs with doxorubicin/ifosfamide in combination but can be diminished with the use of human granulocyte-macrophage colony stimulating factor.
Another regime with activity in patients with metastatic STS is MAID, a combination of mesna, doxorubicin, ifosfamide, and dacarbazine. Response rates in approximately half of all patients treated have been reported using this combination. Ongoing clinical trials comparing single agent and combination chemotherapies will further define the appropriate therapy for patients with stage IV disease.
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