Adjuvant radio-chemotherapy with 5-fluorouracil and leucovorin in stage II and III rectal cancer:: 12 months vs. 6 months of therapy -: A study of the Association for Medical Oncology of the German Cancer Society

Background: Postoperative radio-chemotherapy has been established as standard treatment for stage II and III rectal cancer patients. However, modulation and schedule of administration of 5-fluorouracil (5-FU) therapy are still subject of discussion. In a prospectively randomized study we compared 12 vs. 6 months of 5-FU/leucovorin (LV) chemo-radiotherapy in locally advanced or node-positive rectal cancer. Patients and Methods: Patients with stage II and III rectal cancer were postoperatively stratified according to tumor stage and type of operation and randomly assigned to one of two treatment arms: Patients in arm A received a total of 12, patients in arm B a total of 6 cycles of 5-FU (450 mg/m(2)) and LV (100 mg/m(2)), days 1-5, every 4 weeks. During the 2nd cycle local radiation up to 50.4 Gy was performed and dose-reduced chemotherapy (5-FU 350 mg/m(2)) was administered weekly. Study endpoints were disease-free and overall survival as well as toxicity. Results: From 1993 to 1997 263 patients were enrolled in the study. 40 patients had to be excluded from analysis, leaving 223 patients available for evaluation. After a median follow-up of 34.4 months, tumor relapse was seen in 89/223 (39.9%) patients, 11/223 (4.9%) patients presented with local recurrence only, 60/223 (26.9%) with distant metastases only and 18/223 (8.1%) with both local and distant relapse. 61/223 (27.4%) of the patients had died. With respect to disease-free survival (p=0.77) and overall survival (p=0.24), no statistically significant differences in the two treatment arms were observed. Furthermore, testing the equivalence of the 3-year recurrence rates and 3-year survival rates in the two treatment arms showed statistically significant equivalence for recurrence (p=0.03) and survival rates (p=0.03). As reported previously, there is no increase in toxicity with the 12-month regimen. Conclusions: Our results indicate that prolonged chemotherapeutic treatment over 12 months has no relevant advantage over a 6-month protocol with 5-FU and medium-dose LV. The combination of 5-FU and medium-dose LV is well tolerated by the majority of patients, and even prolonged therapy is not associated with increased toxicity.