Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit the process of cell division, and have shown antitumor activity in the treatment of AGC as a single or combination chemotherapy. Accordingly, this review focuses on the efficacy and tolerability of

more »

... anes in the first-or second-line chemotherapy setting for AGC. Molecules 2016, 21, 651 2 of 10 Overview of First-and Second-Line Chemotherapy for AGC Platinum-based doublet chemotherapy has been universally accepted as the standard first-line treatment for AGC in many countries [8] . S-1 is an oral anticancer agent that is a combination of gimeracil, oteracil, and tegafur. Tegafur is a prodrug of 5FU, while gimeracil inhibits the degradation of 5FU by blocking a dehydrogenase enzyme and oteracil reduces the production of 5FU in the gut (Table 1) [9]. In a randomized phase III trial (SPIRITS trial) that compared S-1 plus cisplatin with S-1 alone in 298 patients with AGC, treatment with S-1 plus cisplatin was associated with improved median progression-free survival (PFS) (6.0 vs. 4.0 months) and overall survival (OS) (13.0 vs. 11.0 months), respectively. Plus, the response (54% vs. 31%) was also higher [10]. Therefore, based on this trial, an S-1 plus cisplatin combination regimen has been established as the standard first-line treatment for AGC in Japan. Meanwhile, another large randomized phase III trial (REAL-2 trial), conducted in Western countries, compared capecitabine with 5FU and oxaliplatin with cisplatin in 1003 patients with AGC. The results from this trial indicated that capecitabine is non-inferior to infused 5FU and oxaliplatin is non-inferior to cisplatin, respectively [11] . Plus, the ML17032 phase III trial also evaluated the combination of capecitabine and cisplatin vs. the combination of 5FU and cisplatin in AGC patients [12] . Here, the median PFS (5.6 vs. 5.0 months) and OS (10.5 vs. 9.3 months) were comparable in both groups. Consequently, an oral 5FU (capeciatbine or S-1) and platinum-based combination is now invariably used worldwide as the first-line choice for patients with AGC. Moreover, a more recent phase III trial showed that the addition of trastuzumab to a cisplatin-based chemotherapy significantly improved the survival of patients with HER2-positive AGC [13] . Thus, while the frequency of HER2 overexpression is low (10%-20%), a cytotoxic chemotherapeutic regimen with trastuzumab is regarded as the standard first-line treatment for HER2-positive AGC. In clinical practice, various new chemotherapeutic agents, including oral 5FU, docetaxel, paclitaxel, and irinotecan, have been tested as a second-line chemotherapy. In particular, paclitaxel, docetaxel, and irinotecan have been identified promising drugs whether in combination regimens or as single agents. According to the results of several recent studies, the patient response rates ranged from approximately 10% to 20%, and the PFS ranged from 2.5 to 4.0 months [14] . Interestingly, the survival period following the failure of first-line chemotherapy has been shown to be longer in Asia than in Western countries, possibly due to the higher proportion of patients who receive subsequent chemotherapy in Asia and differences in the patient characteristics [15] .