ACUTE TREATMENT-RELATED DIARRHEA DURING POSTOPERATIVE ADJUVANT THERAPY FOR HIGH-RISK RECTAL-CARCINOMA

Purpose: The combination of pelvic radiotherapy and 5-fluorouracil-bas ed chemotherapy is associated with an increase in acute gastrointestin al toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have l imited their analysis to presenting rates of severe and life-threateni ng diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a p rior clinical trial of adjuvant therapy for rectal cancer. Methods and Materials: In a multiinstitutional clinical trial, 204 eligible patie nts with rectal carcinoma that either was deeply invasive (T3-T4) or i nvolved regional lymph nodes were randomized to receive either postope rative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherap y and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed p rospectively. Results: For the 99 eligible patients who received pelvi c radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea durin g treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligi ble patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2 %, respectively. The increased rates of diarrhea during adjuvant recta l therapy were manifested across all toxicity levels for patients rece iving chemotherapy and pelvic radiotherapy. Of primary clinical import ance is the substantial increase in severe or life-threatening diarrhe a (Grade 3 or more) (22 vs. 4%, p = 0.001) Additionally, increased rat es of any diarrhea and also severe or life-threatening diarrhea were o bserved in patients who had a low anterior resection compared with tho se who had an abdominoperineal resection (p < 0.001 and p = 0.006, res pectively). Conclusion: These results will be of value as a baseline f or investigators who want to use treatment toxicity as an end point in cancer control or cancer therapy trials utilizing similar treatment t echniques. Patients receiving 5-fluorouracil and pelvic radiotherapy c ompared with patients receiving pelvic radiotherapy alone and patients with a prior history of a low anterior resection compared with patien ts who had a prior history of an abdominoperineal resection experience d increased rates of Grades 1 through 4 acute treatment-related diarrh ea, and the most important increase occurred as Grade 3 toxicity. (C) 1998 Elsevier Science Inc.