New Option for Metastatic Colorectal Cancer: Oxaliplatin and Novel Oral S-1 Combination Chemotherapy

The combination of oxaliplatin or irinotecan with bolus and infusional fluorouracil (FU) and folinic acid (FA) is considered the standard regimen for the first-line treatment of metastatic colorectal cancer [1–4]. However, this regimen is inconvenient owing to its requirement for continuous infusion of FU via vascular access. To overcome this drawback, oral fluoropyrimidines such as capecitabine have been used as a substitute for infused FU/FA [5], and recent data have shown that capecitabine plus oxaliplatin (XELOX) was not inferior to infused FU/FA plus oxaliplatin (known as FOLFOX-4 or FUOX) [6, 7]. S-1, a novel dihydropyrimidine dehydrogenase-inhibitory oral fluoropyrimidine, has been used widely in patients with gastric cancer. In phase II studies, S-1 as a single agent showed an overall response rate (ORR) of 19–40% with tolerable toxicities in the first-line treatment of metastatic colorectal cancer [8-10]. To explore the possibility of using S-1 to replace the continuous FU infusion of the FOLFOX regimen, Korean investigators carried out a phase II clinical trial [11] and Japanese investigators performed a phase I/II clinical trial [12] with a regimen of oxaliplatin plus S-1 (OS) for the first-line treatment of metastatic colorectal cancer, respectively.