A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma.

BACKGROUND: Reports of in vitro experiments in colorectal carcinoma cells suggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined with relatively low concentrations of leucovorin (LV) provides optimal enhancement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-hour infusion of high dose 5-FU combined with a relatively low dose of LV was used to treat patients with advanced colorectal carcinoma. METHODS: Thirty-six patients with advanced colorectal carcinoma received 5-FU, 2600 mg/m2, admixed with LV, 100 mg/m2, in a portable infusion pump administered intravenously over a 24-hour period. High dose 5-FU/LV was delivered once a week for 5 consecutive weeks followed by a 1-week recovery period. All patients were assessable for toxicity and response. RESULTS: Two complete responses and 15 partial responses were observed (response rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median response duration was 9.6 months. The median survival and time to progression were 11.9 months and 7.1 months, respectively. The toxicity was mild and acceptable. The major dose-limiting factors were hand-foot syndrome and fatigue. CONCLUSIONS: This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients with advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its correlation with response and toxicity is warranted.

Biofeedback therapy for excessive stool frequency and incontinence following anterior resection or total colectomy.

PURPOSE: Excessive stool frequency and incontinence after anterior resection (AR) or total colectomy (TC) can be refractory to expectancy and antidiarrheal agents. We prospectively assessed efficacy of anorectal biofeedback therapy (BF) in this clinical situation. METHODS: Thirteen patients (10 men and 3 women; mean age, 62.1 (standard error of the mean (SEM), 4.6) years) had more than six bowel movements per day and/or episodes of incontinence, which did not abate after antidiarrheal agents were given for at least six (mean, 27.9 (SEM, 6.3)) months after surgery. All underwent four sessions of outpatient BF. Assessment was by continence questionnaire and anorectal physiology tests, which were administered before and after BF. RESULTS: In seven AR patients, daily stool frequency was decreased (8.7 (SEM, 2.1) before and 4.6 (SEM, 1.2) after, P < 0.05), and daily incontinence episodes were reduced (2.7 (SEM, 0.9) before and 0.4 (SEM, 0.2) after, P < 0.05) after BF. Six TC patients also had decreased daily stool frequency (6.2 (SEM, 2.1) before, 3.3 (SEM, 1.6) after; P < 0.05) and incontinence episodes (2.4 (SEM, 0.9) before, 0.5 (SEM, 1) after; P < 0.05) after BF. There were no significant changes in anorectal physiology parameters after BF. At a mean follow-up of 10.6 (SEM, 2.5) months after BF, there were no regressions or complications. CONCLUSIONS: BF is a safe and effective option for refractory excessive stool frequency and/or incontinence following AR or TC.