In this project, a series of highly focused and innovative trials is proposed. These studies have the potential for immediate impact on the therapy of human soft tissue sarcoma, and are based on observations made in the investigator's The clinical studies follow two themes; (a) intensification of chemotherapy by isolated lung perfusion (Ilp) and (b) tumor vaccines. The investigators have demonstrated the efficiency and feasibility of isolated lung perfusion in a rat sarcoma model. They propose a phase I trial of escalating doses of doxorubicin by ILP in patients with unresectable lung metastases. When the MTD is defined, a phase II adjuvant trial for patients whose metastases have been resected is planned. As experience is gained, platinum analog and combinations will be evaluated in additional phase I and II trials. Detailed pharmacokinetic studies will be conducted as part of these trials. In continuation of their observations regarding ganglioside expression on soft tissue sarcoma, the investigators propose a pilot trial of a combined GDC/GM2 vaccine using an adjuvant that was highly successful in patients with melanoma. Assuming immunogenicity is confirmed, a prospective randomized trial of this vaccine will be conducted in patients with resected, high-risk sarcoma. These studies integrate well with other projects. Tumor tissue resected at the time of lung perfusion will be assayed for TP53, RB, and MDR-1 to provide insights onto mechanisms of resistance, where as novel biologic observations made in project 3 and 5 can be rapidly translated into clinical trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Sloan-Kettering Institute for Cancer Research
New York
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