Preliminary analysis of a randomized clinical trial of adjuvant postoperative RT vs. postoperative RT plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer

Objectives: Two-hundred eighteen patients with TNM stage II-III resectable rectal cancer, enrolled into a randomized clinical trial, were assessed for efficacy and toxicity of adjuvant postoperative radiation therapy (RT) vs, those of combined RT and chemotherapy (CT), with 5-fluorouracil (5-FU) plu s levamisole. End points were overall survival, disease-free survival, the rate of locoregional recurrence, and treatment-related toxicity. Methods: Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/m(2)/d ay intravenous bolus, days 1-5) plus levamisole (150 mg/day orally, days 1- 3); postoperative RT was delivered during week 2 at the same dosage and sch edule as in arm I. The other five cycles of CT (5-FU every 28 days and leva misole every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were normal. Results: RT was completed or modified in 170 (90%) of 189 evaluable patient s undergoing RT (both treatment groups). Only 44 (59%) of 75 evaluable pati ents of arm II completed or had an adjustment of the CT schedule; the remai ning 31 patients (41%) had to stop or never started the CT regimen. Patient s undergoing combined RT and CT had more severe toxicity (enteritis, P = 0. 03). There was one CT-related death (gastrointestinal bleeding) in this sub set. No significant difference was observed in outcome of patients in the t wo study groups, nor for pattern of recurrence (heterogeneity chi (2) = 4.8 2; d.f. = 2; P = 0.08). Conclusions: These preliminary findings suggest a similar efficacy, coupled with less morbidity, of postoperative RT alone compared with a combined re gimen of postoperative RT and CT in patients undergoing radical surgery for stage II-III rectal cancer. J. Surg. Oncol. 2000;75:80-88. (C) 2000 Wiley- Liss, Inc.