[Gastrointestinal cancer and oral anticancer agents]

5-FU has been very valuable as an anticancer agent since it was first developed by Heidelberger in 1957. For over 40 years it has been used either by itself or in combination therapy for the treatment of patients with all types of malignant tumors. To date, no better anticancer agent has been developed for the treatment of patients with gastrointestinal tract cancer. During administration, consideration for a combined regimen from the standpoints of dose intensity, schedule dependency, and biochemical modulation can improve the antitumor effectiveness of 5-FU. It has been found to be most effective if administered by long term (if possible, 4 weeks or more) intravenous or intraarterial continuous drip infusion. However, there are also negative aspects. The dose-limiting toxicity with drip infusions brings about gastrointestinal disorders such as stomatitis and diarrhea. Furthermore, the possibility of trouble and difficulty in managing a catheter kept in the body over long periods not only greatly reduces the patient's QOL, it is also very inconvenient for the patient and increases medical costs. Since the development of oral FT by Kimura, however, many 5-FU prodrugs and masked compounds have been developed in Japan. The aim has been to see how far the concentration of 5-FU in the blood and cancer tissues could be raised. UFT, 5'-DFUR, and HCFU have been developed as derivatives of 5-FU, and these are widely used clinically either alone or in combination therapy. With the aim of further improving antitumor effectiveness and reducing side effects, these compounds have been improved from the viewpoints of pharmacodynamics and pharmalokinetics, based on biochemical modulation, to create S-1 and Capecitabine. Although these are still currently undergoing clinical trials, sufficient results have already been obtained. Cisplatin and CPT-11 are effective for use in the gastrointestinal tract, and much work is going on now to allow these to be taken orally. Future prospects indeed look bright.