Protracted (Continuous 5-Fluorouracil) Infusion with Concomitant Radiation Therapy: Indications and Results

Abstract

The favorable therapeutic exploitation by the combination of two cytotoxic agents, namely ionizing radiation and an antimetabolite, in this case the fluorianted pyrimidine, 5-fluorouracil, (5-FU), has been attempted over the past 25 years with variable success. After the discovery of a synergistic effect on cancers in laboratory animals by this combination therapy (Heidelberger et al. 1958), clinical trials in the early 1960s with 5-FU and radiotherapy showed only moderate success, and in some trials there was no superiority over irradiation alone. Nevertheless, investigation continued until the pioneering work at the Mayo Clinic (Moertel et al. 1969) which provided the guidelines for the maximum permissible dose of 5-FU administered by rapid intravenous injection with radiotherapy. Clinical studies using these guidelines ensued in the 1970s and 1980s and a majority of the nonrandomized and randomized trials for patients with adenocarcinomas of the gastrointestinal tract demonstrated a benefit in local control and survival for those receiving chemoradiation (Schein et al. 1982). More recently, interest has grown in using 5-FU given as a continuous infusion employing either short (96–120 h) or protracted (more than 30 days) infusion schedules combined with conventionally fractionated irradiation (“chemoradiation”) (Rich et al. 1985b). In this chapter, emphasis will be placed on the use of protracted infusion 5-FU in the Department of Clinical Radiotherapy at M.D. Anderson Cancer Center (MDACC), Houston, Texas.