RELATIONSHIP OF ACUTE GASTROINTESTINAL TOXICITY AND THE VOLUME OF IRRADIATED SMALL-BOWEL IN PATIENTS RECEIVING COMBINED-MODALITY THERAPY FOR RECTAL-CANCER

Purpose: To determine the relationship between acute gastrointestinal (Gl) toxicity during the combined modality segment and the volume of s mall bowel in the pelvic radiation field in patients who receive eithe r preoperative or postoperative therapy for rectal cancer. Patients an d Methods: The patient population was derived from four consecutive ph ase I dose-escalation trials. Combined modality therapy included fluor ouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation. Results: Twenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation fie ld as compared with 60 who received preoperative therapy (462+/-129 v 212+/-44 cm(3), P=.002). The most significant relationship between acu te GI toxicity and volume of small bowel was seen in 12 patients who w ere treated on the preoperative sequential low-dose LV trial, all of w hom received the maximum-tolerated dose (MTD) of 5-FU. The volume of s mall bowel in patients who experienced grade 3+ toxicity wets 731+/-27 4 cm(3), as compared with 145+/-58 in those who experienced grade 0 to 2 toxicity (P=.005). Likewise, logistic regression analysis showed th at 26 patients who received the MTD of 5-FU had the most significant a ssociation between GI toxicity and volume of small bowel (P=.036). Con clusion: Our data suggest that the volume of small bowel in the pelvic radiation field may be dose-limiting in the delivery of high-dose 5-F U when combined with LV and radiation therapy. (C) 1995 by American So ciety of Clinical Oncology.