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Fluorouracil + pegylated liposomal doxorubicin + hyperthermia is a combination therapy regimen investigated by The University of Texas Health Science Center, Houston, for the treatment of advanced gynecological and breast malignancies. The regimen consists of the antimetabolite fluorouracil (5-FU), which inhibits thymidylate synthase to disrupt DNA synthesis, and pegylated liposomal doxorubicin, an anthracycline that intercalates DNA and inhibits topoisomerase II. These chemotherapeutic agents are administered in conjunction with mild whole-body hyperthermia (WBH), a procedure that raises the body temperature to approximately 39.5-41.0°C. The rationale for adding hyperthermia is to increase blood flow and vascular permeability within the tumor microenvironment, thereby enhancing the delivery and cytotoxic efficacy of the liposomal and small-molecule drugs. This approach has been evaluated in Phase I/II clinical trials for patients with metastatic breast, ovarian, endometrial, and cervical cancers.
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