Toxicity studies of adjuvant intravenous versus intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer.

Clinical studies were prospectively conducted to quantitate the toxic side-effects of 5-FU administered by either the intravenous (i.v.) or intraperitoneal (i.p.) route. Sixty-six patients were treated following resection of a primary large bowel cancer after randomization to receive 5-FU by i.p. or i.v. routes. In both groups of patients, the dose of drug was increased a fixed amount until a toxic response occurred. At this point, the dose of drug was maintained or reduced in an attempt to complete 12 monthly treatment cycles of chemotherapy. The overall mean dose of drug administered by the i.p. route (1,479 mg) was significantly greater than given i.v. (1,019 mg), as it was for each treatment cycle. The primary adverse side-effect, resulting in drug dose stabilization or reduction, was leukocyte suppression of i.v. 5-FU or physical symptoms (abdominal pain or discomfort) for i.p. 5-FU (p2 = 0.0006 and p2 = 0.0318, respectively). The most frequent symptom reported by all patients was fatigue. Even though i.v. 5-FU dose was titrated to reduce toxicity, the nadir leukocyte count was suppressed over all cycles. The total numbers of immediate and delayed serious complications that resulted from i.v. or i.p. 5-FU were similar, although the nature of these complications differed markedly between the two routes of drug administration. Failure to complete 5-FU chemotherapy was significantly more common if patients received i.v. 5-FU plus pelvic irradiation. These studies indicate that intraperitoneal 5-FU administration decreases systemic drug effects even when the i.p. drug dose is increased to cause local toxicity.

RCT Entities:   Population Interventions Outcomes