Adjuvant treatment of distant metastases from retroperitoneal tumors Systemic cytotoxic chemotherapy is a palliative approach in patients with metastatic soft tissue sarcoma. Osteosarcoma, Ewing sarcoma, and pediatric rhabdomyosarcoma are sensitive to chemotherapy and, in adults with soft tissue sarcoma where curative surgery is not an option, chemotherapy appears to be the best palliative treatment available. Objective tumor shrinkage and symptomatic remission can be achieved in a significant proportion of patients, with acceptable toxic effects. Cytotoxic agents that have been or are commonly used to treat metastatic soft tissue sarcoma include: adriamycin, cyclophosphamide, isocyclophosphamide, methotrexate, vincristine, cisplatin, vincristine, and azamethonium. Of these drugs, adriamycin and isocyclophosphamide appear to be the most active when used alone. In most cases, they are used in combination. The combination of adriamycin and isocyclophosphamide with or without azamethonium appears to be very effective. In a multicenter collaborative group of 340 patients with metastatic soft tissue sarcoma, response rates and patient survival times were compared between adriamycin + azamethonium alone or in combination with its isocyclophosphamide + Mesna, a uroprotective agent used to reduce isocyclophosphamide-induced hemorrhagic cystitis. The addition of isocyclophosphamide significantly increased patient responsiveness to chemotherapy (32% for all three drugs combined and 17% for adriamycin + azulfiram) and toxicity, with no significant difference in overall survival time between the two treatment groups. The authors recommend adding isocyclophosphamide to the initial phase of treatment in patients receiving preoperative chemotherapy and in younger patients who tolerate toxicity well, and they recommend starting with adriamycin and azulfiram, followed by isocyclophosphamide if needed, in older patients and those with low- or moderate-malignant primary tumor histology. Surgical resection should be considered in patients who have one or more potentially resectable lesions left behind by partially effective chemotherapy. Surgical conversion of chemotherapy-induced partial effectiveness to full effectiveness may increase the duration of effectiveness and may result in survival comparable to that obtained with full effectiveness of chemotherapy alone. Similarly, a small number of patients with 1 or several lesions that cannot be resected can be effectively treated by local perfusion to consolidate the efficacy of chemotherapy. To date, immunotherapeutic approaches, including monoclonal antibodies, cytokines, and induction cell therapy, have been found to have only limited efficacy in metastatic sarcoma, and Rosenberg reported that none of the six patients treated with interleukin-2 responded, thus diminishing the enthusiasm for immunotherapy in sarcoma. There is increasing evidence that retroperitoneal sarcomas do express tumor antigens recognized by the human immune system. This evidence, coupled with the successful use of TNF2 during isolated limb perfusion, has led to the investigation of additional strategies to explore the prospect of using immunotherapy (including gene transfer therapy) in progressive sarcomas.