RESUMEN
Objective A phase Ⅰ study was conducted to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity(DLT) of chemotherapy of oral doxifluridine(5-dFUR) and leucovorin with concurrent standard radiotherapy(RT) as adjuvant treatment in patients with rectal cancer. Methods Patients aged 18-75 years old, Karnofsky scored ≥70%, stage Ⅱ/Ⅲ rectal cancer after curative surgery were eligible. Total RT dose was delivered as DT 50 Gy in the fraction of 2.0 Gy per day for 5 weeks to the pelvic area. 5-dFUR was administered concurrently with radiotherapy in escalating doses, and oral leucovorin was The DLTs included grade 3 or grade 4 hematologic and nonhematologic toxicity. Results From Aug. 2005 the most common side effects although all neutropenia was less grade 3. The DLT was observed in 1 patient of RT. In the following 3 enrolled patients, one suffered grade 3 abdominal cramp pain, diarrhea, fatigue, nausea/vomit and grade 2 neutropinea and fever. Grade 3 diarrhea was also observed in all the additional 3 papatients didn't complete the scheduled concurrent chemoradiotherapy due to severe side effects,including 1 at grade 3 abdominal cramp pain,fatigue and nausea/vomit. Conclusions Diarrhea is the most common and severe side effect in this phase Ⅰ study. The MTD of doxifluridine, concurrently with RT and fixed dose of oral cramp pain is often accompanied with diarrhea and nauser/vomit when the dose of doxifluridine exceeds 550 mg/( m2 · d) or 900 mg/d,patients need to be observed carefully.