• R D Marsh, N M Chu, J N Vauthey, W M Mendenhall, G Y Lauwers, C Bewsher, and E M Copeland.
• Division of Hematology/Oncology, College of Medicine, University of Florida, Galnesville 32610-0277, USA.
• Cancer. 1996 Jul 15; 78 (2): 217-25.

BackgroundThis study was designed to determine the efficacy and maximally tolerated dose of 5-fluorouracil when administered by chronobiologically shaped prolonged infusion in combination with radiation therapy in patients with both locally advanced and unresectable rectal carcinoma.MethodsEighteen sequential patients determined clinically to have either locally advanced or unresectable rectal carcinoma were treated by 4500 centigray (cGy) or 5580 cGy, respectively, combined with continuous chronobiologically modulated 5-FU infusion starting at 250 mg/m2/day, with the dose escalating in each cohort of 5 patients if no Grade 3 or higher toxicity was observed in each cohort. Imaging studies were obtained prior to and after completion of treatment.ResultsAll 18 patients completed the full course of radiation therapy and all were subsequently resectable for potential cure. The maximum tolerated dose of 5-FU was 275/m2/day for 5 weeks. Seven patients had a sphincter-sparing procedure, and ten patients underwent an abdominoperineal resection, all with clear margins. Five complete pathologic responses (28%) were obtained. The average follow-up time was 12 months with a range of 6 to 37 months. With the exception of two patients, one of whom declined surgery and one of whom died of widespread disease, all of the patients have remained free of disease.ConclusionsThe combination of radiation therapy and continuous chronobiologically shaped 5-FU infusion at a dose of up to 275/m2/day is well tolerated and appears to be more effective in downsizing and possibly downstaging locally advanced and unresectable rectal carcinoma than radiation therapy alone. Longer follow-up will determine whether ultimate disease free and overall survival are improved by this method.

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