Oral drugs in the treatment of metastatic colorectal cancer

Intravenous administration of fluoropyrimidine-based chemotherapy has been the cornerstone of treatment in metastatic colorectal cancer (mCRC) for decades. The availability of oral capecitabine has improved the tolerability in monotherapy schedules, and has simplified combination schedules. Since then, other oral drugs have proven efficacy in this setting. We review the available evidence and most recent data concerning oral drugs with proven efficacy in mCRC, including capecitabine, S-1, trifluridine-tipiracil (TAS-102) and regorafenib. The use of capecitabine is widely implemented in the care of mCRC. However, with recent data supporting its prolonged use, the relatively high incidence of hand-foot syndrome (HFS) may impair quality of life. In Asian populations, S-1 is associated with equivalent efficacy but lower incidence of HFS compared to capecitabine. Further studies evaluating the effects of S-1 in Western populations are needed. Both regorafenib and TAS-102 improve the overall survival of patients in whom all other treatment options have failed. Since only a subset of patients appears to benefit, future studies to identify predictive biomarkers are needed