Trials of adjuvant chemotherapy in colorectal cancer

Chemotherapy has been extensively investigated in colorectal cancer. Evaluation in advanced disease has shown that only a limited number of drugs are active. This activity was assessed according to objective criteria for response of measurable lesions, but despite producing objective remissions, no agent has prolonged survival in advanced disease. Drugs showing activity in advanced disease have been evaluated subsequently as adjuvants to surgery. Single agents were evaluated first and 5-fluorouracil has been investigated most extensively. It has been administered by a variety of routes and in different regimens and in some trials it has produced results which border on statistical significance for both disease-free interval and survival. It is the drug of first choice in colorectal cancer, although in some trials no effect was seen. Razoxane (ICRF 159) has also been evaluated and has shown some promise, although also some toxicity. Trials of combinations of treatments have been performed and have used permutations of 5-fluorouracil, MeCCNU, BCG and radiotherapy. None of these trials has shown a definite advantage for chemotherapy and, in some, toxicity has been considerable. 5-Fluorouracil as a single agent has shown the best results to date, and is the treatment of first choice but no treatment has been shown to prolong survival unequivocally in colorectal cancer. Future trials should include a surgery-only control arm, against which any new treatment can be compared.