[Surgical treatment for advanced gastric cancer]. Retrospective comparison of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (modified FAM) combination chemotherapy versus palliative therapy in treatment of advanced gastric cancer. Clinical efficacy of S-1 combined with cisplatin for advanced gastric cancer Efficacy and safety of docetaxel or epirubicin, combined with cisplatin and fluorouracil (DCF and ECF), regimens as first line chemotherapy for advanced gastric cancer: a retrospective analysis from Turkey. Extensive Intraoperative Peritoneal Lavage as a Standard Prophylactic Strategy for Peritoneal Recurrence in Patients with Gastric Carcinoma Targeted HER2 Treatment in Advanced Gastric Cancer Retrospective Evaluation of the Efficacy of First-Line Treatment of Advanced Gastric Cancer With Docetaxel and Oxaliplatin Comprehensive analysis of Excision repair complementation group 1, Glutathione S-transferase, Thymidylate synthase, and Uridine diphosphate glucuronosyltransferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI. Weekly treatment with irinotecan, folinic acid and infusional 5-fluorouracil (ILF) in patients with advanced gastric cancer Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. Survival results of a randomised two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) followed by D2 gastrectomy for resectable advanced gastric cancer. Short-term curative effect of S-1 plus oxaliplatin as perioperative chemotherapy for locally advanced gastric cancer: a prospective comparison study. Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: a first-line phase II study. A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Neoadjuvant chemotherapy versus surgery alone for locally advanced gastric cancer: a retrospective comparative study. Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. A randomized, comparative study of combination chemotherapies in advanced gastric cancer: 5-fluorouracil and cisplatin (FP) versus 5-fluorouracil, cisplatin, and 4'-epirubicin (FPEPIR). Kyoto Research Group for Chemotherapy of Gastric Cancer (KRGCGC). Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer Impact of palliative gastrectomy in patients with incurable advanced gastric cancer. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.
Despite the incidence of gastric cancer is decreasing , it remains the fourth most common malignancy and the second leading cause of cancer-related death around the world . The prognosis of gastric cancer is still poor and surgery is the mainstay treatment . Lymph node dissection plays an important role in the surgery of gastric cancer due to the high incidence of lymph node metastasis and recurrence . There has been a consensus between the West and the East that D2 lymph node dissection is the st and ard dissection for advanced gastric cancer . Some clinical trials have showed good results of  neoadjuvant chemotherapy  in advanced gastric cancer . Large sample r and omized controlled studies are needed to confirm the value of neoadjuvant chemotherapy About one-third of patients with gastric cancer are unresectable at the time of diagnosis . Their median survival is < 6 months , with a grave prognosis . The purpose of this study was to assess the efficacy of a modified FAM ( mFAM ) regimen in advanced gastric cancer . We retrospectively review ed the clinical records of 409 advanced gastric cancer patients who had not received curative surgery . Among 409 patients , 202 patients were treated with an mFAM regimen ( infusional 5-FU + doxorubocin + mitomycin-C )  , and 207 patients received no chemotherapy ( control group ) .  No differences were found in clinical parameters between the two groups . The 1-year survival rates were 34.1 % for the mFAM-treated group and 22.5 % for the control group ( p = 0.0135 ) . In subset analysis , a higher 1-year survival rate was demonstrated in patients with mFAM and palliative surgery . Of the 154 evaluable patients in the mFAM-treated group , the response rate was 17.5 % . In these patients , median response duration was 30 weeks , and progression-free survival was 23 weeks . Overall toxicity of mFAM regimen was relatively tolerable and reversible . In conclusion , FAM combination chemotherapy , which has been used as a st and ard therapy , prolonged survival after modification of the administration schedule and combination with palliative surgery . A prospect i ve r and omized study is warranted to confirm this conclusion from our retrospective study Several chemotherapy regimens used against advanced gastric cancer have been studied extensively over the decades in an attempt to further improve the prognosis of patients . To date , no st and ard chemotherapeutic regimens have been established worldwide . S-1 ( TS-1 ® ) , a combination of ftorafur and two modulators , gimestat ( CDHP ) and oxonic acid , in a molar ratio of 1 : 0.4 : 1 , has been widely used in Japan for the treatment of advanced gastric cancer , and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs . We treated 12 patients with advanced gastric cancer with 80 mg/m2 of S-1 for 21 days and 60 mg/m2 of cisplatin ( CDDP ) on day 8 every 5 weeks . The treatment was continued until disease progression , unacceptable toxicity , or the patient 's refusal . Eight out of 12 evaluable patients achieved a partial response ( PR ) , with a response rate of 66.7 % . The incidence of grade 3 or 4 adverse effects , including myelosuppression and gastrointestinal toxicities , was 16.6 % . None of the patients treated with this regimen died of adverse effects and none required hospitalization for the toxicity . We conclude that the combination of S-1 and CDDP seems to have a high therapeutic index , enhancing the antitumor effect of S-1 while maintaining modest adverse effects , thus suggesting the possible use of this combination based at the outpatient clinic ( apart from a short stay in hospital during the infusion of CDDP with hydration ) . Further study with a large number of patients may be needed to confirm the combination of S-1 and CDDP to be an appropriate first-line chemotherapy for gastric cancer OBJECTIVES Advanced gastric cancer ( AGC ) patients have a poor prognosis . The best benefit of chemotherapy is usually achieved by first line setting . Very few studies have compared combination regimens . This study was design ed to compare two combination regimens . METHODS Patients with advanced gastric cancer receiving first line chemotherapy were retrospectively collected , and divided into two groups , receiving DCF ( docetaxel , cisplatin and fluorouracil ) or ECF ( epirubicin , cisplatin and fluorouracil ) regimens . Data were collected for the retrospective analysis in a single center . RESULTS Eighty-six patients were eligible for analysis . Median overall survival ( OS ) was 10.0 months in the ECF group and 11.0 months in the DCF group ( p=0.31 ) . Median progression free survival ( PFS ) for ECF and DCF was equal at 6.0 months . Second line chemotherapy were administered in more than one third of patients . Both regimens had similar toxicity . CONCLUSIONS This is the first study investigating the outcomes of gastric cancer chemotherapy in this region . ECF and DCF regimens have similar efficacy and a similar tolerability profile for first line treatment of advanced gastric cancer . The decision of the first line chemotherapy in advanced gastric cancer could be improved with patient selection according to clinical parameters and molecular markers Objective : This prospect i ve r and omized multicenter study aims to evaluate the efficacy of extensive intraoperative peritoneal lavage followed by intraperitoneal chemotherapy ( EIPL-IPC ) on the overall 5-year survival of advanced gastric cancer patients with intraperitoneal free cancer cells without overt peritoneal metastasis ( CY+/P− ) . The study also aims to determine the merit and reliability of EIPL-IPC therapy as a prophylactic strategy for peritoneal metastasis . Summary Background Data : Although the prognosis of advanced gastric cancer patients with CY+/P− is extremely poor , a suitable st and ard regimen for treating such patients has not yet been established . Methods : A total of 88 patients with CY+/P− from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were r and omly allocated to 3 groups : surgery alone group , surgery plus intraperitoneal chemotherapy ( IPC ) group , and surgery plus EIPL and IPC ( EIPL-IPC ) group . Prognostic significance of EIPL-IPC therapy was evaluated by Kaplan-Meier curves , and its value as an independent prognostic factor was assessed by univariate and multivariate analyses . Results : The overall 5-year survival rate of the patients with EIPL-IPC was 43.8 % , and this data were significantly better than that of the IPC group ( 4.6 % , P < 0.0001 ) and the surgery alone group ( 0 % , P < 0.0001 ) . Among various recurrent patterns , the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence than both of the other groups ( P < 0.0001 ) . Univariate and multivariate analyses revealed that EIPL was the most significant impact factor . Conclusions : The present study clearly revealed that EIPL-IPC therapy significantly improved the 5-year survival span of advanced gastric cancer patients with CY+/P−.  Thus , EIPL-IPC therapy is strongly recommended as a st and ard prophylactic strategy for peritoneal dissemination Amplification of the HER2 gene and over-expression of the HER2 protein in gastric cancer have been shown in a large number of studies . HER2 positivity can be detected in approximately 20 % of patients , which is a characteristic associated with poor prognosis . Pre clinical in vitro and in vivo studies have demonstrated that both trastuzumab and lapatinib are effective in different gastric cancer models and have thus lead to the initiation of clinical studies . In the first phase III study , the ToGA trial , HER2-positive patients with advanced gastroesophageal and gastric adenocarcinoma were r and omized to receive 5-fluorouracil/capecitabine and cisplatin either alone or in combination with trastuzumab . A statically significant gain in overall survival was seen in the patients who received the combined treatment of trastuzumab and chemotherapy . It is expected that the encouraging results from the ToGA trial will have an immediate impact on the management of patients and that routine HER2 testing of patients with advanced gastric cancer will be initiated within a relatively short period of time The incidence rate of gastric cancer is highest in China , where 5 in 10 new cases of stomach cancer across the world are diagnosed . Even though surgical management is the treatment of choice , it is not significantly effective due to advanced stage of the disease at diagnosis and the increased chances of primary tumor recurrence and metastasis to secondary organs . First-line chemotherapy of advanced gastric cancer patients recommend oxaliplatin and docetaxel ; however , not much is known about their usage in Chinese patients . Therefore we retrospectively analyzed 199 cases of advanced gastric cancer ( intestinal , diffuse , and mixed types ) receiving either docetaxel or oxaliplatin-based first-line chemotherapy .  The end-points determined were objective response rate ( ORR , sum of complete and partial responses ) , disease control rate ( DCR , sum of complete response , partial response , and stable disease ) , median progression-free survival ( mPFS ) , and median overall survival ( OS ) time . Both docetaxel and oxaliplatin-based chemotherapy exhibited improved ORR and DCR ; however , the comparison of short-term objective efficacy ( ORR and DCR ) was not statistically significant ( p > .05 ) between the two groups . Our results indicated that PFS and OS of intestinal-type gastric cancer were extended compared with diffuse-type and mixed-type gastric cancer . Adverse reactions were within the control range and after symptomatic treatment were significantly ameliorated . Both docetaxel and oxaliplatin-based chemotherapy thus had a robust treatment outcome and can prospect ively be used as one of the effective chemotherapy regimens for advanced gastric cancer patients in China e15580 Background : Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens . Oxaliplatin and irinotecan have shown to be effective in the treatment of gastric cancer . We assessed whether single nucleotide polymorphisms ( SNPs ) in ERCC1 , GST , TS , and UGT1A1predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy .  METHODS Total genomic DNA was extracted from whole blood of patient . The PCR- restriction fragment length polymorphism ( RFLP ) method was applied to detect the known variant sites of ERCC1 , GST , TS , and UGT1A1 . RESULTS Response rate of FOLFOX ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed 34.7 % and 16 % , respectively . TTP and OS of 1st line administration of FOLFOX ( N=35 ) was 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) . Only the GSTM1 positive genotype showed a significantly better time to progression ( P=0.023 ) . But significant genotype variation of TS , GST and ERCC1,which assumed to affect to activity of oxaliplatin was not observed to RR , toxicity , and overall survival . Response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed 55.4 % and 9.5 % , respectively . TTP and OS of 1st line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5months ) . Low expression type ( 2R/2R , 2R/3C , and 3C/3C ) of TS was associated with high incidence of grade ≥3 neutropenia . But significant genotype variation of UGT1A1,which assumed to affect to toxicity of irinotecan was not observed to RR , toxicity , and survival . CONCLUSIONS In this study , GSTM1 positive genotype showed a significantly better time to progression in the advanced gastric cancer treated with FOLFOX . Low expression type ( 2R/2R , 2R/3C , and 3C/3C ) of TS was associated with high incidence of grade ≥3 neutropenia in the advanced gastric cancer treated with FOLFIRI . Well design ed prospect i ve trial will be clearly identifying relations between chemotherapy and genetic variations . No significant financial relationships to disclose Although 5-fluorouracil remains the mainstay of treatment for advanced gastric cancer ( AGC ) , no st and ard chemotherapy regimen exists . Combinations of irinotecan with folinic acid and infusional 5-fluorouracil ( 5-FU ) ( ILF ) have shown good efficacy with acceptable toxicity in patients with metastatic colorectal cancer . At present , only sparse data on ILF are available for AGC . Therefore we conducted a prospect i ve study of this combination in 25 consecutive patients with metastatic gastric cancer . Median age was 63 years , 10 had received prior chemotherapy and 13 presented initially with peritoneal carcinosis . Treatment consisted of irinotecan 80 mg/m2 , folinic acid 500 mg/m2 and infusional 5-FU 2.0 g/m2 over 24 h , given weekly for 6 weeks followed by a 1-week rest . Grade 3/4 hematologic toxicity occurred in six patients ( anemia = 4 , neutropenia = 1 and leukopenia = 1 ) . Non-hematologic toxicity consisted mainly of nausea/vomiting ( grade 3/4 in six patients ) and diarrhea ( grade 3/4 in 10 patients ) . The overall response rate was 20 % for first- and second-line treatment , with two complete and three partial responses . Another nine patients ( 36 % ) had stable disease , for a tumor control rate of 56 % . Median time to progression was 4 months , median overall survival and survival for patients with tumor control was 7 and 13 months , respectively . We conclude that ILF is a feasible outpatient regimen with manageable toxicity that provides tumor control in a high proportion of patients with advanced gastric cancer , even among those with unfavorable prognostic features Results of 6589 gastric cancer operations at the Department of Surgery , Seoul National University Hospital , from 1970 to 1990 were reported . About two thirds ( 76.6 % ) were advanced gastric cancer ( stages III and IV ) . The 5-year survival rate of operated stage III gastric cancer was only 30.6 % , with frequent recurrence . Conversely , cell-mediated immunities of advanced gastric cancer patients were significantly decreased . Therefore , to improve the cure rate and to prevent or delay recurrence , curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy ( immunochemosurgery ) in stage III patients . To evaluate the effect of immunochemosurgery , two r and omized trials were studied in 1976 and 1981 . In first trial , 5-fluorouracil , mitomycin C , and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used . The 5-year survival rates for surgery alone ( n = 64 ) and immunochemosurgery ( n = 73 ) were 23.4 % and 44.6 % , respectively , a significant difference . In the second trial , there were three groups : group I , immunochemosurgery ( n = 159 ) ; group II , surgery and chemotherapy ( n = 77 ) ; and group III , surgery alone ( n = 94 ) . 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years . The 5-year survival rate of group I was 45.3 % , significantly higher than the 29.8 % of group II and than the 24.4 % of group III . The postoperative 1-chloro-2.4-dinitrobenzene test , T-lymphocyte percentage , phytohemagglutinin- and con-A-stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group . Therefore , immunochemosurgery is the best multimodality treatment for advanced gastric cancer BACKGROUND The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy . Both S-1 plus cisplatin ( SC ) and paclitaxel plus cisplatin ( PC ) are promising regimens as neoadjuvant chemotherapy ; however , the optimal duration remains unclear . PATIENTS AND METHODS In this 2 × 2 r and omised phase II trial , stage III gastric cancer patients , those with a prognosis corresponding to stage III , and macroscopically resectable stage IV cases were r and omised to two or four courses of  S-1 ( 80 mg/m(2 ) for 21 d with 1 week rest)/cisplatin ( 60 mg/m(2 ) at day 8) or PC ( 80 and 25 mg/m(2 ) , respectively , on days 1 , 8 , and 15 with 1 week rest ) as neoadjuvant chemotherapy . The primary end-point was the 3-year overall survival ( OS ) . RESULTS Between October 2009 and July 2011 , 83 patients received 2 courses of SC ( n=21 ) , 4 courses of SC ( n=20 ) , 2 courses of PC  ( n=21 ) and 4 courses of PC ( n=21 ) . The 3-year OS was 60.9 % for SC and 64.3 % for PC and 64.3 % for the two courses and 61.0 % for the four courses . Subset analyses demonstrated no subgroup which showed any potential survival benefit  by PC in comparison to SC or by four courses as in comparison to two courses . CONCLUSIONS Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer . CLINICAL TRIAL NUMBER UMIN-000002595 This research aim ed to investigate the efficacy of S-1 plus oxaliplatin ( SOX ) as perioperative chemotherapy for locally advanced gastric cancer . We enrolled 102 patients with preoperative clinical stage T3 - 4N × M0 gastric cancer who were then r and omly assigned to receive SOX as either perioperative chemotherapy ( group A , 50 patients ) or postoperative adjuvant chemotherapy ( group B , 52 patients ) . Short-term curative efficacy and adverse effects of perioperative chemotherapy were analyzed . The rates of R0 resection , surgical complications , combined multiple organ resection , overall survival ( OS ) , and disease-free survival ( DFS ) were compared between the groups . Results showed an overall response rate in group A of 42 % , with a disease control rate of 94 % and a tumor down-staging rate of 50 % . An R0 resection rate of 90 % was achieved in group A , which was significantly higher than that in group B ( 75 % ) . No surgical mortality was observed , and the differences in surgical complications and combined multiple organ resection rates between the groups were not significant . The postoperative pathological examination of 4 patients in group A did not show any cancer cells in the tumor bed , result ing in a histological complete remission rate of 8 % . The average OS and DFS for group A patients were 17.928 and 16.134 months , respectively , which were both longer than that of group B patients . However , the differences were not significant . In all , our results shows that in locally advanced gastric carcinoma , SOX perioperative chemotherapy is effective and results in a significantly improved R0 resection rate compared to postoperative SOX administration . Perioperative SOX does not cause additional surgical complications and has low adverse reaction rates ; moreover , it appears to prolong survival OBJECTIVE To evaluate the effects of continuous hyperthermic peritoneal perfusion ( CHPP ) together with st and ard chemotherapy on the prognosis of patients with gastric cancer invading the serosa . DESIGN Retrospective study . SETTING University hospital , Japan . SUBJECTS 174 patients who had undergone curative resection for gastric cancer invading the serosa ( T3 ) between 1980 and 1989 , 78 of whom had been r and omised to be treated with CHPP after operation and 96 who received st and ard chemotherapy .  INTERVENTIONS CHPP was done immediately after operation ; 8 - 10 l fluid containing 80 - 100 mg/m2 mitomycin C was perfused at a rate of 100 - 200 ml/minute , and inflow and out flow temperatures were maintained at 44 - 45 degrees C and 40 - 42 degrees C , respectively . This was followed by a st and ard regimen of mitomycin C and 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil ( 1:4 ) ( UFT ) . The control group received the st and ard regimen only . MAIN OUTCOME MEASURES Five year survival and patterns of recurrence in three groups : no lymph node metastases , 1 - 9 , and 10 or more . RESULTS Only in the group with 1 - 9 lymph node metastases was there an appreciable but not significant difference in 5 year survival : 66 % compared with 44 % ( p = 0.084 ) . The mean disease free survival for patients with peritoneal metastases was 30 months in the CHPP group compared with 23 months among the controls . CONCLUSION CHPP improved prognosis in patients with T3 gastric cancer who had only 1 - 9 metastatic lymph nodes OBJECTIVE Current chemotherapy protocol s for gastric cancer present high toxicity . The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients . DESIGN In this multicenter non-r and omized phase II trial , we administered the FOLFIRI chemotherapy protocol ( irinotecan [ 180 mg/m(2 ) ] , fluorouracil [ 5-FU ] [ 400 mg/m(2 ) ] and folinic acid 400 mg/m(2 ) or 200mg/m(2 ) of l-folinic acid ) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment ( CGA ) . Responses were assessed at 2 months . RESULTS Forty-two patients received eight cycles of the FOLFIRI regimen , with 82.5 % of patients showing disease control : 10 patients ( 26 % ) showing objective ( partial or complete ) responses and 23 ( 57.5 % ) showing stable disease . One-year overall survival ( OS ) was 41.5 % [ 95%CI 26.5 - 56.0 ] and one-year progression-free survival ( PFS ) was 31.8 % [ 95%CI 18.4 - 46.1 % ] . We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia . CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment . CONCLUSIONS Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly Purpose The combination of docetaxel , cisplatin , and S-1 ( DCS ) chemotherapy is expected to be a promising regimen for advanced gastric cancer . This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer . Methods Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 ( 40 mg/m2 b.i.d . ) on days 1–14 and docetaxel ( 60 mg/m2 ) plus cisplatin ( 60 mg/m2 ) on day 8 every 3 weeks , followed by st and ard curative surgery within 4–8 weeks . The primary endpoint was R0 resectability . Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 ( ERCC1 ) in the pretreated tumor tissues was examined by immunohistochemistry . Results A total of 43 patients received neoadjuvant chemotherapy . The response rate was 74.4 % , and disease control ratio was 100 % . Grade 4 neutropenia developed in 53.5 % of patients and febrile neutropenia in 16.3 % . Non-hematological grade 3/4 adverse events were anorexia ( 23.3 % ) , nausea ( 14.0 % ) , and diarrhea ( 23.3 % ) , but these were generally transient and manageable . The proportion of R0 resections in the 43 eligible patients was 90.7 % , and a pathological response was found in 65.9 % of patients . There were no treatment-related deaths and no major surgical complications . The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5 % . Conclusions Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities . The DDB2/ERCC1-high phenotype , as determined by immunohistochemistry , may be useful predictor of resistance to DCS chemotherapy BACKGROUND Chemotherapy is the st and ard of care for incurable advanced gastric cancer . Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric cancer with a single non-curable factor remains controversial . We aim ed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients . METHODS We did an open-label , r and omised , phase 3 trial at 44 centres or hospitals in Japan , South Korea , and Singapore . Patients aged 20 - 75 years with advanced gastric cancer with a single non-curable factor confined to either the liver ( H1 ) , peritoneum ( P1 ) , or para-aortic lymph nodes ( 16a1/b2 ) were r and omly assigned ( 1:1 ) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution , clinical nodal status , and non-curable factor . Patients , treating physicians , and individuals who assessed outcomes and analysed data were not masked to treatment assignment . Chemotherapy consisted of oral S-1 80 mg/m(2 ) per day on days 1 - 21 and cisplatin 60 mg/m(2 ) on day 8 of every 5-week cycle . Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions . The primary endpoint was overall survival , analysed by intention to treat . This study is registered with UMIN-CTR , number UMIN000001012 . FINDINGS Between Feb 4 , 2008 , and Sept 17 , 2013 , 175 patients were r and omly assigned to chemotherapy alone ( 86 patients ) or gastrectomy followed by chemotherapy ( 89 patients ) . After the first interim analysis on Sept 14 , 2013 , the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13·2 % , so the study was closed on the basis of futility . Overall survival at 2 years for all r and omly assigned patients was 31·7 % ( 95 % CI 21·7 - 42·2 ) for patients assigned to chemotherapy alone compared with 25·1 % ( 16·2 - 34·9 ) for those assigned to gastrectomy plus  chemotherapy . Median overall survival was 16·6 months ( 95 % CI 13·7 - 19·8 ) for patients assigned to chemotherapy alone and 14·3 months ( 11·8 - 16·3 ) for those assigned to gastrectomy plus chemotherapy ( hazard ratio 1·09 , 95 % CI 0·78 - 1·52 ; one-sided p=0·70 ) . The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone  : leucopenia ( 14 patients [ 18 % ] vs two [ 3 % ] ) , anorexia ( 22 [ 29 % ] vs nine [ 12 % ] ) , nausea ( 11 [ 15 % ] vs four [ 5 % ] ) , and hyponatraemia ( seven [ 9 % ] vs four [ 5 % ] ) . One treatment-related death occurred in a patient assigned to chemotherapy alone  ( sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy ) and one occurred in a patient assigned to chemotherapy plus gastrectomy  ( rapid growth of peritoneal metastasis after discharge 12 days after surgery ) . INTERPRETATION Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor , gastrectomy can not be justified for treatment of patients with these tumours . FUNDING The Ministry of Health , Labour and Welfare of Japan and the Korean Gastric Cancer Association BACKGROUND / AIMS Preoperative chemotherapy is considered an effective treatment option for patients with gastric cancer . We retrospectively evaluated neoadjuvant chemotherapy with oxaliplatin , leucovorin and 5-flurouracil ( OLF ) in patients with locally advanced gastric cancer to determine its feasibility , as well as impact on the curative resection rate and patients ' survival . METHODOLOGY A total of 87 patients with locally advanced gastric cancer that underwent preoperative chemotherapy combined with surgery or surgery alone were r and omly matched according to the clinical TNM stage . The clinical responses to chemotherapy were assessed . The curative rate , postoperative complications and patients ' survival between both groups were compared . RESULTS The two groups were well matched . Complete or partial response was observed in 51.7 % ( 15/29 ) of patients in the OLF group , and three ( 10.3 % ) of them had complete pathologic response . The curative resection rates were 89.7 % in the OLF group and 77.6 % in the surgery alone group . The postoperative complications were equal for both groups . The mean survival is 20.6 months in the OLF group vs. 19.9 months in the surgery alone group ( p=0.02 ) . CONCLUSIONS Neoadjuvant chemotherapy using OLF combination is active in gastric cancer and the toxicity level is acceptable . This treatment improves the curative resection rate and patients ' survival in locally advanced gastric cancer Background Despite curative resection , 50%–90 % of gastric cancer patients die of disease relapse . Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities , more recent studies have not been able to define the st and ard treatment for advanced gastric cancer . The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG ( bacille Calmette-Guérin ) and FAM ( 5-fluorouracil , adriamycin , mitomycin C ) chemotherapy on the survival of  patients with locally advanced resectable gastric cancer . Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were r and omly assigned to three treatment groups : BCG + FAM ( immunochemotherapy ) , FAM ( chemotherapy ) , and control ( surgery only ) . Treatment was continued for 2 years or until death . Further postsurgical follow up was carried on for up to 10 years . Results Overall 10-year survival was 47.1 % for the immunochemotherapy group ( P < 0.037 vs FAM and P < 0.0006 vs control ) , 30 % for the chemotherapy group ( vs control , NS ) , and 15.2 % for the control group . In patients with pT2/T3 primary tumors , 10-year survival was 55.3 % for BCG + FAM vs 28.2 % for FAM ( P < 0.01 ) and 14.6 % for the control group ( P < 0.00018 ) . BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer . Immunochemotherapy was well tolerated . Conclusion This study , based on a limited number of patients , indicates that adjuvant immunochemotherapy ( BCG + FAM ) may prolong the survival of gastric cancer patients after curative gastrectomy ; in particular , in patients with pT2/T3 tumors and intestinal-type primary tumors . There was no survival benefit from FAM adjuvant chemotherapy The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2 - 169 combined with chemotherapy in patients with advanced gastric cancer . HLA-A 2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1 - 1084 and VEGFR2 - 169 combined with S-1 and cisplatin . The study included 22 patients ( median age 60.5 years ) who received at least one cycle of the combination therapy .  No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients . Twelve patients ( 55 % ) showed partial response and 10 had stable disease after two cycles of the combination therapy . The disease control rate ( partial response and stable disease ) was 100 % after two cycles . The median time to progression was 9.6 months and median overall survival was 14.2 months . VEGFR1 - 1084-specific cytotoxic T lymphocyte ( CTL ) response was induced in 18 ( 82 % ) of the 22 patients and VEGFR2 - 169-specific CTL response was induced in 18 ( 82 % ) of the 22 patients . Patients showing CTL response to VEGFR2 - 169 peptide had significantly better prognosis than those without , as demonstrated by the overall survival ( OS ) and time to progression ( TTP ) ( OS , p=0.028 , TTP , p=0.006 ) . The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer . Substantial specific CTL for both peptides was frequently induced even under chemotherapy . Thus , cancer vaccination combined with st and ard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer Sixty patients with inoperable or recurrent gastric cancers were r and omly assigned into 2 treatment regimens : the FP regimen , consisting of cisplatin ( CDDP , 50 mg/body , d1 ) + 5-fluorouracil ( 5-FU , 250 mg/body , d2-d5 ) , or the FPEPIR regimen , CDDP+5-FU ( FP ) + 4'-epirubicin ( EPIR , 30 mg/m2 , d2 ) , administered intravenously every 2 weeks . The objective responses were evaluated in 43 patients ( FP : 21 ; FPEPIR : 22 ) . The response rates were 24 % ( 5PR/21 ) for FP and 27 % ( 6PR/22 ) for FPEPIR . Objective responses were seen in 1 primary lesion and 4 metastatic lesions in patients on the FP regimen , and in 3 primary lesions and 4 metastatic lesions in patients on the FPEPIR regimen . The 6 month and 1 year survival rates were 34 % and 13 % for FP , and 55 % and 27 % for FPEPIR , respectively ( not significant ) . Significantly higher survival rates were demonstrated in those patients with recurrent cancers ( p < 0.01 ) and those who responded to the FPEPIR regimen ( p < 0.05 ) . Drug toxicities were assessed in 56 patients , and were in general mild and well tolerated . However , the FP regimen induced significantly less neutropenia ( p < 0.01 ) and less complete alopecia ( p < 0.01 ) than the did FPEPIR regimen . These results suggest that FPEPIR may be a more beneficial regimen for the treatment of gastric cancer than FP , and may be indicated for further clinical trials Background This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin ( DXP ) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer . Methods Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine ( days 1–14 ) and intravenous docetaxel and cisplatin ( day 1 ) every 3 weeks . Results In the phase I study , 15 patients were treated with 4 different dose levels . Asthenia and neutropenic fever were the dose-limiting toxicities . For the phase II study , 1,125 mg/m2 of capecitabine was initially recommended with 60 mg/m2 docetaxel and 60 mg/m2 cisplatin . However , frequent dose modifications at this dose level result ed in a final optimal dose of 937.5 mg/m2 capecitabine . Among the 40 patients enrolled in the phase II study , 4 complete and 23 partial responses were observed , presenting objective response rate of 68 % . Ten patients achieving good response with complete disappearance of distant metastases underwent surgery , and 4 pathologic complete responses were identified . After the median follow-up of 83.7 months ( range , 20.2–86.5 ) in surviving patients , the median overall survival was 14.4 months and median progression-free survival was 7.6 months . The most frequent grade 3/4 adverse events were neutropenia ( 62.5 % ) and asthenia ( 37.5 % ) . Ten per cent of the patients experienced neutropenic fever , with one case of sepsis-induced death . Conclusion DXP displays considerable antitumor activity , and may thus present effective first-line treatment for advanced gastric cancer . Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant setting s is warranted BACKGROUND The efficacy of palliative gastrectomy for incurable advanced gastric cancer remains debatable . PATIENTS AND METHODS The study group comprised a series of 164 patients who had undergone palliative gastrectomy .  Survival and prognostic factors were evaluated by univariate and multivariate analyses . RESULTS The median survival time was 9 months . Univariate analysis identified the following as factors that adversely affected survival : larger and deeper undifferentiated tumors ; peritoneal , hematogenous , or remaining lymph-node metastasis ; a large number of non-curative factors ; less extensive lymph-node dissection ; and an absence of chemotherapy . The Cox proportional regression hazard model recognized histological type , hematogenous metastasis , peritoneal metastasis and chemotherapy as independent factors . Moreover , the number of non-curative factors independently affected the disease-specific survival . In patients with a single non-curative factor , histological type and adjuvant chemotherapy were independent prognostic factors . CONCLUSION A r and omized controlled study should be conducted in advanced gastric cancer patients with a single non-curative factor to confirm the usefulness of palliative gastrectomy followed by chemotherapy shown here BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS  ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer .  Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . )
Within a combination chemotherapy regimen , oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is , epirubicin-cisplatin-capecitabine is preferred over the prior st and ard regimen , epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine ( eox ) is a reasonable alternative to ecf .
QUESTION What is the optimal chemotherapy regimen in advanced gastric cancer ?
PERSPECTIVES Gastric cancer is the second leading cause of cancer mortality worldwide .
Despite low incidence rates for gastric cancer in Ontario , the overall prognosis is bleak , with 5-year survival rates of approximately 23 % in Canada .
Even with the considerable body of research available on chemotherapy for advanced gastric cancer , uncertainty remains .
There is no recognized st and ard treatment , and there appears to be geographic variation in practice .