Pathologic downstaging of T3-4NX rectal cancer after chemoradiation:: 5-fluorouracil vs. Tegafur

Purpose: To describe downstaging effects in locally advanced rectal cancer induced by 2 fluopirimidine radiosensitizing agents given through different routes in conjunction with preoperative radiotherapy. Methods and Materials: From March 1995 to December 1999, two consecutive groups of patients with cT(3-4)N(x) rectal cancer (94% CT scan, 71% endorectal ultrasound) were treated with either (1) 45-50 Gy (1.8 Gy/day, 25 fractions) and 5-fluorouracil (5-FU) (500-1,000 mg/m(2) by 24-h continuous i.v. infusion on Days 1-4 and 21-25) or (2) oral Tegafur (1,200 mg/day on Days 1-35, including weekends). Surgery was performed 4 to 6 weeks after the completion of chemoradiation. Results: The total T downstaging rate was 46% in the 5-FU group and 53% in the Tegafur group. Subcategories were downstaged by the sensitizing agents (5-FU vs. Tegafur) as follows: pT(0-1), 14% vs. 23%; pT(2), 32% vs. 32%; pT(3), 49% vs. 37%; pT(4), 5% vs. 7%; and N-0, 74% vs. 86%. Analysis of residual malignant disease in the specimen discriminated mic/mac subgroups (mic: <20% of microscopic cancer residue), with evident superior downstaging effects in the Tegafur-treated group: pTmic 23% vs. 58% (p = 0.002). Conclusions: When administered concurrent with pelvic irradiation, oral Tegafur induced downstaging rates in both T and N categories superior to those induced by intermediate doses of 5-FU by continuous i.v. infusion. In this pilot experience, oral Tegafur reproduced the characteristics of downstaging described previously when full doses of 5-FU have been combined with radiotherapy. (C) 2001 Elsevier Science Inc.