5-Fluorouracil radiation sensitization — A brief review

Summary 5-Fluorouracil (FUra) has emerged as the most promising clinical radiosensitizer now available. FUra's capacity to render human cells more sensitive to x-rays was established soon after its synthesis. However, the recognition that the drug's unusual pharmacology dictated explicit scheduling requirements in man was not realized until recently when work in the author's laboratory identified the extra-cellular drug concentration X time factors necessary to create the intra-cellular radiosensitive state. Subsequent clinico-pharmacologic investigations led to the realization that only prolonged continuous infusions combined with appropriately fractionated, cyclical radiation therapy would maximize the clinical utility of this approach. Infused FUra radiation-sensitization therapy reaches its maximum efficacy against the squamous-transitional cancers. This group of human malignancies comprises about 15% of all human cancers. Preliminary data also suggests substantial promise in the local/regional control of rectal and breast cancers. Infused FUra used as a radiosensitizer has the potential to eliminate the need for about 90% of all radical cancer surgery.