Oral chemotherapeutic agents for gastric and colorectal cancer

Abstract

This manuscript describes the progress of preclinical and clinical development of oral fluoropyrimidines and their modulators for gastric and colorectal cancer. 5-fluorouracil (5-FU) has been the mainstay of systemic therapy since its initial development 40 years ago for gastrointestinal cancer. Recently, there have been many reports indicating higher response either by itself or in combination therapy. One direction is the development of orally administered fluoropyrimidines that maintain or improve upon the effectiveness of intravenous 5-FU. Against the background of increased attention to patient quality of life issues, orally formulated chemotherapy represents a potential major advance in patient convenience and pharmacoeconomic issues. Since the development of oral tegafur, many 5-FU prodrugs and masked compounds have been developed in Japan. UFT, doxifluridine and carmofur 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 pharmacokinetics, based on biochemical modulation, to create S-1 and capecitabine. Although these are still currently undergoing clinical trials, sufficient results have already been obtained.