Prospective, randomized trial of intravenous versus intraperitoneal 5-fluorouracil in patients with advanced primary colon or rectal cancer.

No new chemotherapy agents have been developed recently that present hope for improving survival in patients with colon or rectal cancer. We undertook this study to investigate a new route of administering an old drug, 5-fluorouracil (5-FU). Sixty-six patients with advanced primary colon or rectal cancer were randomized to receive 12 cycles with increasing dosages of intravenous (IV) or intraperitoneal (IP) 5-FU; the mean follow-up time was three years. The maximal tolerable dose and objective adverse side effects were prospectively recorded. The mean daily dose of 5-FU given by the IV route was 904 mg; for the IP route it was 1361 mg (p2 less than 0.0001). Two of ten patients had recurrent peritoneal carcinomatosis when treated with IP 5-FU; ten of eleven patients treated with IV 5-FU developed peritoneal implants (p2 less than 0.003). The incidence of serious complications was the same, but hematologic toxicity and hepatic toxicity were significantly reduced in patients who received IP 5-FU. When 5-FU is delivered by the IP route, the tolerable dose of drug was markedly increased without an increase in adverse side effects. The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis but time to relapse and survival was not improved. IP 5-FU may be recommended for investigation in patients with perforated colon cancer, peritoneal implants, or as one part of a multimodality treatment protocol for colorectal cancer. If 5-FU is given to patients with gastrointestinal malignancy, the IP route should be strongly considered.

RCT Entities:   Population Interventions Outcomes