The seminal study showing benefit of combining 5FU with RT as adjuvant therapy for rectal cancer,r studied 666 patients with stage II or III rectal cancer who received intermittent bolus injections or protracted venous infusions of fluorouracil during postoperative radiation to the pelvis. They also received systemic chemotherapy with semustine plus fluorouracil or with fluorouracil alone in a higher dose, both before and after the pelvic irradiation.
With median follow-up of 46 months among surviving patients, patients who received a protracted infusion of fluorouracil had a significantly increased time to relapse (p= 0.01) and improved survival (p= 0.005).
Since that time, it has been standard to add chemotherapy to RT for rectal cancer. The next issue to be studied was the efficacy of preoperative versus postoperative combined modality treatment.
A large randomised Phase III studyr demonstrated that neoadjuvant chemoradiation for rectal cancer improved local control and reduced toxicity but did not improve overall survival compared to postoperative chemoradiation. 5FU was given as a 120 hour continuous infusion at a dose of 1000 mg/m² per day. The overall 5 year survival rates were 76 v 74 % for preoperative v postoperative treatment (p=0.80). The cumulative incidence of local recurrences at five years was 6 % in preoperative group v 13 % in postoperative group (p=0.006) .
Studies are now addressing the question of oral v infusional fluoropyrimidines with RT, and also the role of adding newer agents such as oxaliplatin and irinotecan to the combination.