Rectal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage II Rectal Cancer
Preoperative chemoradiation with fluorouracil (5-FU) for patients with clinically staged T3 or T4 rectal adenocarcinoma.
Total mesorectal excision (TME) with either low anterior resection (LAR) or abdominoperineal resection (APR).
Postoperative chemoradiation for patients with stage II or III rectal cancer who did not receive preoperative chemoradiation.
Four to six months of 5-FU-based chemotherapy postoperatively.
A clinical trial.
Prior to the standard use of preoperative chemoradiation for stage II and III rectal cancer, several studies established the benefits of adjuvant combined-modality therapy for surgical stage II and III disease. Intergroup protocol 86-47-51 (MAYO-864751) demonstrated a 10% improvement in overall survival (OS) with the use of continuous-infusion 5-FU (225 mg/m2 /day throughout the entire course of radiation therapy) compared with bolus 5-FU (500 mg/m2 /day for three consecutive days during the first and fifth weeks of radiation).[Level of evidence: 1iiA] The final results of (CLB-9081) showed no survival or local-control benefit with the addition of leucovorin (LV), levamisole, or both to 5-FU administered postoperatively for patients with stage II and III rectal cancers at a median follow-up of 7.4 years.[Level of evidence: 1iiA]
Incidence and mortality
Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide  and the second leading cause of cancer deaths (irrespective of gender) in the United States. It is estimated that there will be 142,820 new cases diagnosed in the United States in 2013 and 50,830 deaths due to this disease. Between 2005 and 2009, CRC incidence rates in the United States declined by 4.1% per year among adults aged 50 years and older. For the past...
Another study, (INT-0144 [NCT00002551]), was a three-arm randomized trial designed to determine whether continuous-infusion 5-FU throughout the entire standard six-cycle course of adjuvant chemotherapy was more effective than continuous 5-FU only during pelvic radiation and included the following:
Arm 1 received bolus 5-FU in two 5-day cycles before (500 mg/m2 /day) and after (450 mg/m2 /day) radiation therapy, with protracted venous infusion 5-FU (225 mg/m2 /day) during radiation therapy.
Arm 2 received continuous infusion 5-FU before (300 mg/m2 /day for 42 days), after (300 mg/m2 /day for 56 days), and during (225 mg/m2 /day) radiation therapy.
Arm 3 received bolus 5-FU plus LV in two 5-day cycles before (5-FU 425 mg/m2 /day; LV 20 mg/m2 /day) and after (5-FU 380 mg/m2 /day; LV 20 mg/m2 /day) radiation therapy, and bolus 5-FU plus leucovorin (5-FU/LV) (5-FU 400 mg/m2 /day; LV 20 mg/m2 /day; days 1 to 4, every 28 days) during radiation therapy. Levamisole (150 mg/day) was administered in 3-day cycles every 14 days before and after radiation therapy.
Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 55% and 49% of patients in the two bolus arms, respectively (i.e., arms 1 and 3), versus 4% of patients in the continuous-infusion arm. No DFS, OS, or locoregional failure (LRF) difference was detected (across all arms: 3-year DFS, 67% to 69%; 3-year OS, 81% to 83%; LRF, 4.6% to 8%).[Level of evidence: 1iiA]