Page 78 - Read Online
P. 78

Page 2 of 9                                    Eto et al. J Cancer Metastasis Treat 2018;4:23  I  http://dx.doi.org/10.20517/2394-4722.2017.73

               Table 1. Results of trials with chemotherapy for metastatic gastric cancer in Japan
                Authors, year            Regimen           Patients (n)   OS (months)          HR
                Koizumi et al. , 2008   S-1 + cisplatine     148             13.0          0.77 (0.61-0.98)
                         [8]
                                     S-1                     150             11.0          1
                Yamada et al. [33] , 2015   S-1              234             11.4          0.83 (0.68-1.00)
                                     Cisplatine + irinotecan   236           12.3          0.82 (0.68-0.99)
                                     5-FU continuous infusion  234           10.8          1
                Koizumi et al. [34] , 2014   S-1 + docetaxel  314            12.5          0.84 (0.71-0.99)
                                     S-1                     321             10.8          1
                Boku et al. [35] , 2009   S-1                234             11.4          0.83 (0.68-1.00)
                                     Cisplatine + irinotecan   236           12.3          0.82 (0.68-0.99)
                                     5-FU continuous infusion  234           10.8          1
                Narahara et al. [36] , 2011   S-1 + irinotecan  155          12.8          0.93
                                     S-1                     160             10.5          1
                Hironaka et al. [44] , 2013   Weekly paclitaxel   108        9.5           1.13 (0.86-1.49)
                                     Weekly irinotecan       111             8.4           1
                Shitara et al. [45] , 2017   Tri-weekly nab-paclitaxel   247   10.3        1.06 (0.87-1.31)
                                     Weekly nab-paclitaxel   246             11.1          0.97 (0.76-1.23)
                                     Weekly paclitaxel       248             1.06          1
               OS: overall survival; HR: hazard ratio; 5-FU: 5-fluorouracil

               and drugs targeting specific molecular pathways, have achieved an increase in the response rate, it is
               difficult to cure metastatic GC with chemotherapy alone. The current goals of treatment, therefore, are to
               relieve GC-related symptoms and to prolong survival. The median survival time achieved in clinical trials
               for metastatic or recurrent GC remains between 6 and 13 months , although it has been proven that
                                                                         [6-8]
               chemotherapy prolongs survival when compared with the best supportive care (BSC) [9,10] . Recently, it has
               been reported that curative resection may be performed for patients with liver metastasis, para-aortic lymph
               node metastasis, or positive peritoneal cytology, especially when chemotherapy has been effective [11-19] . In
               this review, we summarize the publications and guidelines that have focused on recent progress in the
               treatment of metastatic GC in Japan.



               TREATMENT STRATEGY FOR METASTATIC GC
               The main treatment for metastatic GC is chemotherapy. Table 1 shows the representative trials for metastatic
               or recurrent GC in Japan. The first chemotherapeutic agent of choice against metastatic GC was 5-fluorouracil
               (5-FU), which was used either alone or in combination with various agents. In Japan, 5-FU as a key drug for
               GC was replaced by S-1 (tegafur-gimestat-otastat potassium), based on favorable results in trials involving
               Japanese patients [8,20] . Thereafter, trials focused on identifying the best combination regimen using S-1.
               Recently, many drugs designed to target the molecular pathways involved in the development or progression
               of cancer have been studied for metastatic GC [21-31]  [Table 2]. In patients with GC overexpressing human
               epidermal growth factor receptor 2 (HER2), the addition of trastuzumab, an antibody targeting HER2,
               to the first-line cytotoxic drug regimens significantly prolonged the survival of patients . Therefore, the
                                                                                           [21]
               presence or absence of HER2 overexpression is the first branch point when selecting the treatment regimen.
               The recommended treatment algorithm for patients of metastatic GC in the 5th edition of the Japanese
               Gastric Cancer Treatment Guideline is shown in Figure 1. Recommendation A indicates that the regimen is
               strongly recommended based on the certain evidence while recommendation B suggests that the regimen is
               weakly recommended because of insufficient evidence. Figure 2 demonstrates the alternative algorithm for
               patients who are unfit for the standard treatment due to comorbidities or social situations.


               HER2-negative advanced GC
               In Japan, the first choice of chemotherapy for metastatic GC is S-1 and cisplatin (SP), according to the results
               of a phase III trial (SPIRITS trial ). This trial showed that patients treated with SP had significantly better
                                           [8]
               overall survival (OS) than those treated with S-1 alone, with a median OS of 13 vs. 11 months (P = 0.04).
               Progression-free survival (PFS) was also significantly longer in patients treated with SP than in those treated
   73   74   75   76   77   78   79   80   81   82   83