EFFECTS OF PHARMACOKINETIC MODULATING CHEMOTHERAPY USING ORAL UFT ANDCONTINUOUS VENOUS 5FU INFUSION ON THE PROGNOSIS OF IRRADIATED RECTAL CARCINOMAS WITH P53 OVEREXPRESSION

We previously found that patients with irradiated rectal carcinomas wi th p53 overexpression had poor prognoses after radical resection. in t he present study, we attempted to improve the prognosis by the introdu ction of adjuvant chemotherapy. We administered pharmacokinetic modula ting chemotherapy, based on the concept that the benefit of a continuo us venous 5-fluorouracil (5FU) infusion can he potentiated by low-dose oral UFT, ia combination of 1-(2-tetrahydrofuryl)-5-fluorouracil (teg afur) and uracil at a molar ratio of 1:4. Forty-two of 107 patients ex amined between January 1992 and December 1997 with an irradiated recta l carcinoma (39%) showed positive immunohistochemical staining for p53 . Among them, 14 patients received adjuvant chemotherapy (CT group). T he percentage tf highly malignant tumors in the CT group was higher th an that in the no-chemotherapy (NCT) group (n=28). However, the rate o f cumulative local recurrence in the CT group was 0%, while that in th e NCT group was 28.6% (p=0.0392). The distant recurrence rate in the C T 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 sugg ested that the antitumor property of 5FU enhanced by pharmacokinetic m odulation might have a lethal effect on rectal tumors with a loss of t he p53-related apoptosis pathway. These preliminary findings are encou raging for the treatment of rectal cancers with possible poor prognosi s.