[en] PURPOSE: We report the downstaging, acute toxicity, and preliminary local control and survival of pre-op 5-FU, low dose LV, and concurrent RT followed by post-op LV/5-FU for pts with clinically resectable, T3 rectal cancer. MATERIALS AND METHODS: A total of 32 pts (M:26, F:6) were prospectively treated from 12/91-8/95. Eligibility criteria included adequate hematologic indicies, primary adenocarcinoma limited to the pelvis, and T3 disease confirmed by transrectal ultrasound. Twenty five pts were considered clinically to require an APR on initial (pre-treatment) assessment by their operating surgeon. The median age was 56 (range: 24-80), and the median distance from the anal verge was 5.0cm (range: 3-9cm). Pts received 2 monthly cycles (bolus daily X 5) of LV (20mg/m2) and 5-FU (325mg/m2), beginning concurrently with day 1 of RT, followed by surgery 4-5 weeks later. RT included 4680 cGy to the pelvis followed by a boost to 5040 cGy. Post-operatively, pts received a median of 2 monthly cycles (range: 0-10 cycles) of LV (20 mg/m2) and 5-FU (425mg/m2). A toxicity assessment was performed at each visit using the NCI toxicity criteria modified for gastrointestinal toxicity. The median follow-up was 12 months (range: 3-48 months). All 32 patients were included in the analysis of toxicity, sphincter preservation, and downstaging. Analysis of patterns of failure and survival was limited to the 15 pts who had a minimum follow-up of 1yr or developed failure prior to 1 yr. For this subset the median follow-up was 24 months (range: 3-48 months). RESULTS: During the pre-op segment, individual grade 3+ acute toxicities were; diarrhea: 16%, bowel movements: 16%, leukopenia: 12%. The incidence of total toxicity was 25% ((8(32))). The median nadir counts were; WBC: 2.9 (range: 1.7-5.6), HGB: 12.4 (range: 7.1-15.0), and PLT (X1000): 161 (range: 113-237). The pathologic complete response rate was 9% ((3(32))). An additional 13% ((4(32))) had negative lymph nodes and 1-2 microscopic foci of tumor in the bowel wall (clinical complete response) Therefore, the total complete response rate (clinical + pathologic) was 22% ((7(32))). Operative procedures included LAR: 16, LAR/Coloanal anastomosis: 8, APR: 8. All margins were negative. Of the 25 pts thought to initially require an APR, 17 (68%) were able to undergo sphincter preserving surgery. Of the 25 pts, 5 had involvement of the anal sphincter at initial presentation and pre-op therapy was not performed with the goal of sphincter preservation since an APR was planned regardless of the degree of downstaging. Excluding those 5 pts, the incidence of sphincter preservation would have been (17(20)) (85%). The crude incidence of failure as a component of failure was local: 0%, abdominal: 10% and distant: 3%. The 2 yr actuarial disease free survival was 86% and the overall survival was 100%. CONCLUSION: Our preliminary data reveal encouraging downstaging, acute toxicity, local control, and survival rates. Additional experience is needed in order to assess the long term results. The concurrent low dose LV regimen remains our standard pre-op combined modality approach for pts with clinically resectable T3 rectal cancer