S‐1 plus Raltitrexed for Refractory Metastatic Colorectal Cancer: A Phase II Trial

Lessons Learned. The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5‐fluorouracil (5‐FU) in metastatic colorectal cancer (mCRC) after long exposure to 5‐FU. S‐1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third‐ or later‐line therapy in mCRC.