Preoperative radiation in combination with uracil/tegafur (UFT) and mitomycin C (MMC) in locally advanced rectal adenocarinoma

Abstract

13512 Background: Preoperative chemoradiation has become the standard treatment approach not only for tumor downstaging, but also for adjuvant treatment of locally advanced rectal adenocarcinomas (Sauer et al. NEJM 2004). The most commonly used chemotherapeutic agent with preoperative radiation is either bolus or infusional 5-fluorouracil (5-FU). These combinations produce pathologic complete responses in the range of 10–30%. Continuous infusion of 5-FU has proven to be superior to bolus 5-FU, when given during radiation. However widespread use of continuous infusion 5-FU has been limited by the need for an indwelling venous catheter and portable infusion pump. UFT acting like infusional 5-FU, offers the advantage of oral administration. Response to preoperative chemoradiation is associated with higher sphincter preservation and survival rates. UFT, MMC (a hypoxic cell cytotoxin) combination during preoperative radiation may improve the response rates. The aim of this study is to assess the efficacy (pCR) and toxicity of this combination. Methods: 26 patients with biopsy proven non metastatic rectal adenocarcinoma were included. Clinical T and N stages, determined by pelvic MRI were; 10/26 cT3, 16/26 cT4, 10/26 cN0, and 16/26 cN+. Pelvic radiotherapy was administered with 6 or 15 MV photons to 46 Gy in 23 fractions over 5 weeks, with four field technique in prone position. During radiotherapy, patients received UFT, 300 mg/m2 divided in two daily doses, five days a week, from Monday to Friday, starting on the first day, ending on the last day of radiation, together with bolus injection of MMC, 10 mg/m2, once in the morning of the first day of radiaton. Surgery was performed 6 or more weeks after the radiation treatment has ended. Results: Acute grade III/IV toxicity was observed in 6 out of 26 patients. Diarrhea, 3 grIII, 1 grIV. Neutropenia, 1 grIII. Dermatitis, 1 grIII. Tumor downstaging was observed in 16 patients out of 26 (62%). Nodal sterilization was obtained in 11 patients out of 16 (69%), with a pathologic complete response in 3 out of 26 patients (11%). Conclusions: Preoperative radiation concurrent with UFT and MMC has a good activity, with manageable acute toxicity. No significant financial relationships to disclose.