Suppository delivery of 5-fluorouracil in rectal cancer

Preoperative radiotherapy with concomitant intravenous 5-fluorouracil (5-FU-i.v.) is effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Topical 5-FU application may enhance its radiosensitizing and cytotoxic effects. Suppository and intravenous 5-FU administration were compared with respect to myelo-suppression and tissue concentrations.

Rats received 120 mg/kg 5-FU-i.v. or via suppository (5-FU-S). White blood cell count, serum albumin, alkaline phosphatase, creatinine, and aspartate aminotransferase (AST) were determined before and serially after 5-FU administration. In a separate experiment, rats received 5-FU-S or 5-FU-i.v. as already described. Portal and systemic blood, rectal, iliac lymph node, liver, and lung tissue were harvested for high-performance liquid chromatography determination of 5-FU concentrations 30 min, 1, 3, 6, and 12 h after drug administration.

No toxicity was observed in 5-FU-S animals, whereas 63% of 5-FU-IV animals had diarrhea. Weight loss and myelosuppression occurred only in 5-FU-i.v. animals. Rectal drug concentrations were significantly higher in the 5-FU-S animals compared with 5-FU-i.v. animals, 0.5-6 h after drug administration. Blood, liver, and lung 5-FU concentrations with 5-FU-S were comparable to those with 5-FU-i.v.

5-FU suppositories are associated with fewer systemic side effects and higher rectal 5-FU concentrations than with 5-FU-i.v. administration.