Intraperitoneal 5-fluorouracil infusion for treatment of both peritoneal and liver micrometastases

Pharmacokinetic studies indicate that intraperitoneal administration of 5-fluorouracil (5-FU) has the potential to reduce the locoregional recurrence rate of gastrointestinal cancer. We have tested this hypothesis in a rat model, in which liver and peritoneal micrometastases were induced by the injection of cultured colonic cancer spheroids into both the portal vein and peritoneal cavity, respectively. Sixty-seven tumor-bearing animals were randomized to receive either no treatment, superior mesenteric vein 5-FU, or intraperitoneal 5-FU. Infusions were begun 2 days after tumor inoculation at a dose of 45 mg/kg/day and continued for 5 days. All untreated animals had advanced liver and peritoneal metastases 1 month after tumor implantation. Intraperitoneal 5-FU totally prevented the development of macroscopic tumor on peritoneal surfaces in 57% of animals. Paradoxically, rats treated with portal vein 5-FU had significantly more tumor or peritoneal surfaces than did the untreated group (p = 0.038). Both intraperitoneal and portal vein chemotherapy resulted in approximately a 50% reduction in total liver metastases compared with untreated animals (p = 0.78). Comparison of hepatic tumor growth within different lobes or segments demonstrated that although intraperitoneal 5-FU produced a homogeneous reduction in liver metastases, the effect of portal vein chemotherapy was unevenly distributed. We conclude that intraperitoneal chemotherapy was not only effective in eradicating peritoneal micrometastases but also received the same overall reduction in liver metastases as did portal vein chemotherapy. Moreover, regional differences in hepatic tumor responses as a result of drug streaming during portal vein 5-FU infusion were not observed after intraperitoneal chemotherapy.