Effects of pharmacokinetic modulating chemotherapy using oral UFT and continuous venous 5FU infusion on the prognosis of irradiated rectal carcinomas with p53 overexpression.

We previously found that patients with irradiated rectal carcinomas with p53 overexpression had poor prognoses after radical resection. In the present study, we attempted to improve the prognosis by the introduction of adjuvant chemotherapy. We administered pharmacokinetic modulating chemotherapy, based on the concept that the benefit of a continuous venous 5-fluorouracil (5FU) infusion can be potentiated by low-dose oral UFT, a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4. Forty-two of 107 patients examined between January 1992 and December 1997 with an irradiated rectal carcinoma (39%) showed positive immunohistochemical staining for p53. Among them, 14 patients received adjuvant chemotherapy (CT group). The percentage of highly malignant tumors in the CT group was higher than that in the no-chemotherapy (NCT) group (n=28). However, the rate of cumulative local recurrence in the CT group was 0%, while that in the NCT group was 28.6% (p=0.0392). The distant recurrence rate in the CT group was also significantly lower than that in the NCT group (7.1% vs. 42.9%, p=0.0376). The cumulative 3-year survival rate was 100% in the CT group and 64.3% in the NCT group (p=0.0245). These results suggested that the antitumor property of 5FU enhanced by pharmacokinetic modulation might have a lethal effect on rectal tumors with a loss of the p53-related apoptosis pathway. These preliminary findings are encouraging for the treatment of rectal cancers with possible poor prognosis.