Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provi des several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer, We attempted a Phase II trial of pre operative chemoradiotherapy with doxifluridine plus a low-dose oral leucovo rin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rec tal cancer in this trial, 21 of whom were available for analysis. The patie nts were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhe a, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients), The clinical tumor response was shown in 5 patients ( 23.8%) as a complete response and 13 patients (61.9%) as a partial response . A complete resection with negative resection margin was done in 18 patien ts (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). T he overall downstaging rate in the T- and N-stage groupings was 71.4% (15 p atients). Conclusion: This study demonstrated the efficacy and low toxicity of chemor adiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic ef ficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unres ectable rectal cancer. (C) 2001 Elsevier Science Inc.