Adjuvant chemotherapy for stage II colon cancer: the time has come.

Introduction reductions in stage II patients compared to stage III patients (a measure of significant clinical benefit from adjuvant chemotherapy). These smaller absolute reductions are more Although several large prospective randomized trials have demonstrated benefit from adjuvant chemotherapy in likely to be missed in underpowered trials. Since the last Consensus Development Conference, patients with stage III colon cancer, the value of such therapy is still debated in patients with stage II disease. information has accumulated on the efficacy of leucovorinmodulated 5-fluorouracil (5-FU+LV) in improving diseaseBased on information from clinical trials available in 1990, a U.S. National Institute of Health Consensus Development free and overall survival both in stage III as well as in stage II colon cancer patients. Furthermore, results from Conference recommended that patients with stage III colon cancer should receive adjuvant chemotherapy with 5randomized trials, directly comparing the 5-FU+LV regimen to the 5-FU+LEV regimen, have demonstrated an fluorouracil and levamisole (5-FU+LEV). No specific adjuvant therapy was recommended for patients with stage advantage for the former. Since in some of these trials a considerable proportion of patients (about 40%) presented II colon cancer outside of clinical trials. These recommendations were primarily based on results from a with stage II disease, the effect of treatment by stage could be assessed. No evidence of a differential treatment effect North American Intergroup study (INT 0035) that demonstrated significant survival improvement with the was observed between stage II and stage III patients, indicating that adjuvant chemotherapy was effective in both administration of adjuvant 5-FU+LEV in patients with stage III colon cancer but no similar improvement in patients groups. This newer information challenged the recommendations of the last NIH Consensus Development with stage II disease. The lack of survival benefit in stage II patients was confirmed in a subsequent update of this Conference and sparked a debate on the value of adjuvant chemotherapy in stage II patients. trial, although a similar reduction in recurrence to that documented in stage III patients was observed. Several explanations have been offered for the discrepancy in adjuvant chemotherapy efficacy between stage II and Effect of adjuvant chemotherapy in stage II patients stage III colon cancer patients. It is possible that a true differential chemotherapy effect exists between stage II and The NSABP colon cancer trials stage III patients because of inherent biological differences between these two groups of patients. The more likely Most of the available evidence supporting the efficacy of adjuvant chemotherapy in stage II patients has been explanation, however, is that there is no true difference in adjuvant chemotherapy efficacy between stage II and stage obtained from NSABP trials of adjuvant therapy. The NSABP has included stage II and stage III colon cancer III patients. However, because of the lower event rate in stage II patients, adjuvant clinical trials are generally patients in all its adjuvant chemotherapy trials. These trials compared different adjuvant chemotherapy regimens with underpowered to demonstrate significant survival differences in this subset of patients. According to this each other and with surgery alone. In four such trials (C-01, C-02, C-03 and C-04), a disease-free survival and/ scenario, similar relative reductions in the rate of recurrence and cancer-related mortality in stage II and stage III patients or survival benefit from chemotherapy that reached or approached statistical significance was demonstrated at 5 (a measure of true biological efficacy of adjuvant chemotherapy), would translate to smaller absolute years of follow-up between at least two treatment groups. Overall, 41% of the patients in the four trials had stage II tumours, providing the opportunity to address whether stage II colon cancer patients benefit from adjuvant chemotherapy Correspondence to: Eleftherios P. Mamounas, M.D., 26900 Cedar Road, Beachwood, Ohio 44122. and to what extent when compared to stage III patients.