Neoadjuvant Chemoradiotherapy with 5-Fluorouracil by Bolus

Background:Neoadjuvantchemoradiotherapy(CT- RT) with continuous infusion ( c.i.) 5-fluorouracil (5-FU) before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. Since the presence of cardiomiopathymaycontraindicatec.i.of5-FU,analternative regimen of 5-FU CT-RT was prospectively studied in these patients. Patients and Methods: From October 2000 to December 2006, patients with clinical stage T3 or T4, or node-positive disease were assigned according to their cardiological status to receive weekly 5-FU bolus administration during radiotherapy (RT). The preoperative treatmentconsistedof5,040cGy,deliveredinfractionsof180 cGy per day, five days per week, and 5-FU, given in 15 minutes at a dose of 450 mg/m 2 of body surface area weekly during all radiotherapy. Surgery was performed six weeks after the completion of CT-RT. The primary endpoint was disease-free survival (DFS). Results: Fifty-one patients received preoperative CH-RT.The 2-year OS rate was 92.3% and the 3-year DFS was 87.5%. The five-year cumulative incidence of local relapse was 3.9%. Grade 3 acute toxic effects occurred in 19.6% of the patients; worsening of patient'scardiopathywasneverreported.Conclusion:Patients with cardiopathy developed similar local control and DFS, toxicity and OS with 5-FU administered weekly by bolus as those reported by literature data. Postoperative chemoradiotherapy (CT-RT) for rectal cancer has improved overall survival (OS) and pelvic control (1-4) but only recently, have preoperative trials addressed chemotherapy radiosensitization to reduce locoregional failure. In fact, protracted venous infusion (PVI) of 5-fluorouracil (5-FU) is the more common treatment. Seven phase III trials comparing PVI versus bolus indicated improved response rates (RR) in metastatic disease (5-12); this improvement has raised the possibility that PVI might eradicate subclinical distant metastasis more effectively in the adjuvant and neoadjuvant setting too, improving radiosensitization (13-17). In the Intergroup (INT) 864751 trial, where PVI versus bolus 5-FU were compared, bolus 5- FU was administered before, during and after pelvic radiotherapy (RT) versus the same pre- and post-CT-RT schedule, but with PVI administered with RT. Improved OS and disease-free survival (DFS) were observed with the latter schedule (4).