Background Preoperative radiotherapy is recommended for selectedpatients with rectal cancer. We evaluated the addition of chemotherapyto preoperative radiotherapy and the use of postoperative chemotherapyin the treatment of rectal cancer.
Methods We randomly assigned patients with clinical stage T3or T4 resectable rectal cancer to receive preoperative radiotherapy,preoperative chemoradiotherapy, preoperative radiotherapy andpostoperative chemotherapy, or preoperative chemoradiotherapyand postoperative chemotherapy. Radiotherapy consisted of 45Gy delivered over a period of 5 weeks. One course of chemotherapyconsisted of 350 mg of fluorouracil per square meter of body-surfacearea per day and 20 mg of leucovorin per square meter per day,both given for 5 days. Two courses were combined with preoperativeradiotherapy in the group receiving preoperative chemoradiotherapyand the group receiving preoperative chemoradiotherapy and postoperativechemotherapy; four courses were planned postoperatively in thegroup receiving preoperative radiotherapy and postoperativechemotherapy and the group receiving preoperative chemoradiotherapyand postoperative chemotherapy. The primary end point was overallsurvival.
Results We enrolled 1011 patients in the trial. There was nosignificant difference in overall survival between the groupsthat received chemotherapy preoperatively (P=0.84) and thosethat received it postoperatively (P=0.12). The combined 5-yearoverall survival rate for all four groups was 65.2%. The 5-yearcumulative incidence rates for local recurrences were 8.7%,9.6%, and 7.6% in the groups that received chemotherapy preoperatively,postoperatively, or both, respectively, and 17.1% in the groupthat did not receive chemotherapy (P=0.002). The rate of adherenceto preoperative chemotherapy was 82.0%, and to postoperativechemotherapy was 42.9%.
Conclusions In patients with rectal cancer who receive preoperativeradiotherapy, adding fluorouracil-based chemotherapy preoperativelyor postoperatively has no significant effect on survival. Chemotherapy,regardless of whether it is administered before or after surgery,confers a significant benefit with respect to local control.(ClinicalTrials.gov number, NCT00002523
[ClinicalTrials.gov]
.)
Source Information
From the Department of Radiation Therapy, University of Franche-Comté, Besançon, France (J.-F.B.); European Organization for Research and Treatment of Cancer Data Center, Brussels (L.C.); Department of Radiation Therapy, University François Rabelais, Tours, France (G.C.); Department of Radiation Therapy, Clinic Ste-Catherine, Avignon, France (L.M.); Department of Radiation Therapy, Cancer Center Dijon, Dijon, France (P.M.); Institut for Oncology and Radiology, Belgrade, Serbia (L.R.-J.); Department of Radiation Therapy, University of Poitiers, Poitiers, France (A.D.); Department of Radiation Therapy, Cancer Center Nantes, Nantes, France (E.B.); Department of Radiation Therapy, Rambam Medical Center, Haifa, Israel (A.B.); and Department of Surgery, Cancer Center Strasbourg, Strasbourg, France (J.-C.O.).
Address reprint requests to Dr. Bosset at the Besançon University Hospital, Department of Radiotherapy, Blvd. Fleming, F-25030 Besançon CEDEX, France, or at jean-francois.bosset{at}ufc-chu.univ-fcomte.fr.
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A correction has been published: N Engl J Med 2007;357(7):728.
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