SANDWICH PREOPERATIVE AND POSTOPERATIVE COMBINED CHEMOTHERAPY AND RADIATION IN TETHERED AND FIXED RECTAL-CANCER - IMPACT OF TREATMENT INTENSITY ON LOCAL-CONTROL AND SURVIVAL

Purpose: The present ''sandwich'' preoperative and postoperative chemo therapy and radiation study was undertaken to evaluate the impact of t reatment intensity on the local control and survival in tethered or fi xed rectal adenocarcinoma (T3, 4 NX M0). Methods and Materials: Betwee n 1990 and 1992, 27 patients were treated with this sandwich protocol, Preoperative therapy consisted of 4 weeks of concurrent radiation (40 Gy) and chemotherapy (mitomycin C on day 1, 5-fluorouracil infusion a nd leucovorin on days 1-4 and days 15-18, respectively), and one cycle of bolus 5-fluorouracil and leucovorin chemotherapy. After surgery, t hey received 2 additional weeks of radiation (18 Gy) and 4 days of sim ilar chemotherapy, The outcome was compared to another 54 patients who were treated with our previous preoperative chemoradiation protocol ( mitomycin C, 5-fluorouracil infusion and 40 Gy of pelvic RT). Results: The complete resectability rate was improved from 91% in the preopera tive protocol to 100% in the sandwich protocol, and the pathologic com plete response rate (T0 N0 M0) was increased from 4 to 15%, There was no local recurrence in the sandwich protocol. The 4-year local failure rate was 23 vs. 0% (p = 0.005). The 4-year distant failure rate was 4 7 vs. 28% (p = 0.079). The 2-year and 4-year survival were 63 and 41% for the preoperative protocol, vs, 92 and 72% for the sandwich protoco l, respectively (p = 0.014), There were more treatment-related Grade 2 diarrhea, but not Grade 3/4 diarrhea in the sandwich protocol, Two pa tients (7%) in the sandwich protocol developed late gastrointestinal c omplications. Conclusions: More intensive radiation and chemotherapy a ppeared to improve the resectability, local control, and survival in t ethered and fixed rectal cancers, There was a moderate but acceptable increase in the bowel morbidity. (C) 1997 Elsevier Science Inc.