Localized radiation therapy and simultaneous chemotherapy with uft and low-dose leucovorin as neoadjuvant treatment in-patients with T3-T4 rectal cancer. a phase II study

Abstract

The aim of the study was to determine pathologic complete response rate and toxicity profile of the combination of high-dose preoperative localized radiation therapy and chemotherapy with UFT and leucovorin given simultaneously in patients with T3-T4 rectal cancer. This combination has been demonstrated feasible in a previous phase I study (Hoff, et al, JCO 18: 3529–3534, 2000). Secondary objectives were to assess resectability and sphincter preservation rates. Eligibility included biopsy proven of rectal adenocarcinoma, T3-T4,N0-2,M0 lesions, performance status <2 (ECOG) and adequate liver, renal, hematological and cardiac functions. Staging work-up included colonoscopy or barium enema, chest X-ray, abdominopelvic CT and transrectal ultrasonography. Treatment consisted of radiation therapy at two dose levels: a)PTV1: GTV + 3–5 cm margin, TD 45 Gy at 1.8 Gy/d b)PTV2: GTV + 1–2 cm margin, TD 55 Gy at 2 Gy/d and simultaneously UFT 300 mg/m2/d and leucovorin 60 mg/d, daily during 6 weeks given orally. Surgical resection was performed within 4–6 weeks after treatment. Between January 2001 and November 2003, 40 patients were included into this study. Patients characteristics: age 35–79 (median 64.5); male/female 29/11; T3N0:23, T3N1:15, and T4N1:2. Thirty-seven patients received full dose of radiation (93%) and in one patient UFT was reduced to 150 mg/m2/d. Mean treatment time was 52 days (range 37–62). Overall, 7 patients (17.5%) had grade 3 acute toxicity being mucositis in 4 patients (10%) and anusitis in 3 (7.5%). There was no grade 4 toxicity. Only one patient developed grade 2 neutropenia. Mean time between radiochemotherapy and surgery was 37 days (range 31–55). At the time of analysis, 3 patients are in surgery and therefore are not evaluable for response. Of the 37 remaining patients, 8 achieved pathologic complete response (21,6%) and 20 downstaged (54%). There was microscopical residual tumor in 8 patients. Radical surgery with free margins could be performed in all 37 patients, being sphincter-saving procedures in 3 of the 9 patients with tumor <5 cm from anal verge. Simultaneous high-dose preoperative localized radiation therapy and UFT and leucovorin is feasible with a low toxicity profile. This schedule is highly effective and merits further investigation