Chemotherapy For Advanced Gastric Cancer Research Articles

36. Analysis of S-1/cisplatin combined neoadjuvant chemotherapy for advanced gastric cancer

36. Analysis of S-1/cisplatin combined neoadjuvant chemotherapy for advanced gastric cancer

Shenqi Fuzheng Injection (参芪扶正注射液) for advanced gastric cancer: A systematic review of randomized controlled trials

To evaluate the effectiveness of Shenqi Fuzheng Injection (, SFI) combined with chemotherapy for advanced gastric cancer. Randomized controlled trials (RCTs) from 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 software was applied for data analyses. Thirteen RCTs involving 860 patients met the selection criteria (all articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3-4, oral mucositis at grade 1-2, leucopenia at grade 3-4, and myelo-suppression at grade 1-2. This systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment.

625P - Randomized Phase Ii Study of S-1 Plus Oral Leucovorin (Sl) Versus Sl Plus Oxaliplatin (Sol) Versus S-1 Plus Cisplatin (Sp) in Patients with Advanced Gastric Cancer (Agc):Updated Overall Survival Data

625P - Randomized Phase Ii Study of S-1 Plus Oral Leucovorin (Sl) Versus Sl Plus Oxaliplatin (Sol) Versus S-1 Plus Cisplatin (Sp) in Patients with Advanced Gastric Cancer (Agc):Updated Overall Survival Data

657P - Second- and Third-Line Chemotherapy in Advanced Gastric Cancer: a Real-Life Clinical Picture

ABSTRACT Aim: Chemotherapy is the mainstay of palliative treatment for metastatic or unresectable gastric cancer. Nevertheless, almost all patients (pts) will develop progressive disease after 1st-line treatment. The role of subsequent salvage chemotherapy is not well established, especially outside of clinical trials. Methods: We reviewed 223 pts with histologically proven unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma who received 1st-line chemotherapy at our Institution between August 2004 and December 2013. At the time of progression, 105 (47%) pts received 2nd-line chemotherapy. The choice of 2nd-line schedule was primarily driven by performance status and progression free survival during 1st-line treatment (mPFS1). After 2nd-line failure, 37 pts underwent 3rd-line therapy. Data from medical records were retrospectively analyzed. Results: For 2nd-line treatment, median progression free survival (mPFS2), median overall survival (mOS) and response rate (RR) were 2.9 months (mo), 5.5 mo, and 17%, respectively. The table below summarizes efficacy data with the various schedules used. The mPFS and mOS from starting 3rd-line treatment were 2.4 mo and 5.4 mo, whereas the RR achieved was 6%. Discontinuation due to adverse events occurred in 3% of pts during 2nd-line and 8% of those given 3rd-line. No toxic deaths were registered during treatment. However, fifty percent of pts received 2nd-line chemotherapy with dose reduction ab initio. Summary of 2nd-line efficacy data with the various schedules used Schedule pts (n) RR n (%) mPFS1 (mo) mPFS2 (mo) mOS mo Overall 105 17/101 (17) 7.3 2.9 5.5 Platinum-based 17 8/17 (47) 10.3 4.3 12.5 FOLFIRI 29 5/26 (19) 8.3 4.2 7.3 Taxane 43 3/42 (7) 6.2 2.5 4.1 Other 16 1/15 (7) 7.1 2.8 5.1 Conclusions: In line with the limited prospective data available, 2nd-line chemotherapy was safely administered to almost half of pts progressing under 1st-line and appeared to be moderately effective. Pts with longer mPFS1 were likely to receive platinum-based regimen or FOLFIRI as 2nd-line chemotherapy, obtaining interesting outcomes. After 2nd-line progression, only a small subgroup of pts continued to benefit from further treatment. Further investigations are strongly advocated to improve treatment outcomes in this setting. Disclosure: All authors have declared no conflicts of interest.

635P - Randomized Phase Ii Study of Cpt-11 Vs Ptx Vs Each Combination Chemotherapy with S-1 in Patients with Advanced Gastric Cancer Refractory to S-1 or S-1 Plus Cddp (Ogsg0701)

ABSTRACT Aim: S-1 plus cisplatin (SP) is recognized as standard first-line chemotherapy for advanced gastric cancer (AGC) and S-1 monotherapy is recognized as standard adjuvant chemotherapy for locally AGC in Japan. Taxane and CPT-11 are two main options and a retrospective analysis has reported that S-1 combination chemotherapy extended overall survival (OS), as second-line chemotherapy for AGC refractory to S1-based chemotherapy. Thus, this prospective multicenter phase II study was carried out to examine efficacy and safety comparing CPT-11, PTX, and each combination chemotherapy with S-1 refractory to S-1 or SP. Methods: Patients with AGC after first-line chemotherapy with S-1 or SP, or during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 who confirmed disease progression by imaging were eligible. Patients were randomly divided into four groups by treatment as follows; Group A: CPT-11 150 mg/m2, day1, q14days, Group B: PTX 80 mg/m2, day1, 8,15, q28days, Group C1: CPT-11 80 mg/m2, day1, 15, S-1 80 mg/m2, day1-21, q35days, Group C2: PTX 50 mg/m2, day1, 8, S-1 80 mg/m2, day1-14, q21days. Primary endpoint was OS, and secondary endpoints were progression-free survival (PFS), response rate and safety. Results: From July 2008 to March 2012, 127 patients were enrolled. Reason for terminating the protocol treatment was for progressive disease(PD) in 86/81/86/76 (Group A/B/C1/C2, %), respectively. Median OS was 11.3/11.3/14.6/10.5 months(M) (Group A/B/C1/C2), 11.8 M in Group A + C1 and 11.1 M in Group B + C2 (p = 0.922, HR: 0.981 [0.679-1.419]), and 11.3 M in Group A + B and 11.1 M in Group C1 + C2 (p = 0.808, HR:0.952 [0.643-1.412]), respectively. Median PFS was 3.0/4.4/3.8/3.5 M (Group A/B/C1/C2), 3.6 M in Group A + C1 and 4.1 M in Group B + C2 (p = 0.035, HR:0.674 [0.468-0.972]), and 3.7 M in Group A + B and 3.7 M in Group C1 + C2 (p = 0.931, HR: 1.017 [0.643-1.412]), respectively. Grade 3 or 4 adverse events (Group A/B/C1/C2, %), were leukopenia (12/7/5/0), neutropenia (29/16/24/24), anemia (7/9/14/14), anorexia (10/2/14/10), nausea (7/2/10/5), diarrhea (5/0/10/0), and fatigue (5/2/10/5). Conclusions: The difference in OS between CPT-11 and PTX, and the efficacy of S-1 sequential therapy were not observed in second-line chemotherapy for AGC refractory to S-1 or SP. Disclosure: All authors have declared no conflicts of interest.

Vascular endothelial growth factor a inhibition in gastric cancer.

Angiogenesis is a vital process in the progression and metastasis of solids tumors including gastric adenocarcinoma. Tumors induce angiogenesis by secreting proangiogenic molecules such as vascular endothelial growth factor A (VEGF-A), and VEGF-A inhibition has become a common therapeutic strategy for many cancers. Several drugs targeting the VEGF-A pathway have been approved for clinical use in selected solid tumors, and several anti-VEGF-A strategies have been examined for gastric cancer. Phase II studies suggested that bevacizumab, an anti-VEGF antibody, can increase the efficacy of chemotherapy for advanced gastric cancer, but two international phase III trials failed to show an overall survival benefit. Two more recent international phase III trials have examined ramucirumab, an antibody targeting the primary receptor for VEGF-A, as second-line therapy for advanced gastric cancer and found a survival benefit both as single agent therapy and when combined with chemotherapy. Finally, correlative science studies suggest that the VEGF-A pathway may have varying importance in gastric cancer progression depending on ethnicity or race. This article will review the preclinical and clinical studies on the role of the VEGF-A pathway inhibition in gastric cancer.

Randomized phase II study of CPT-11 versus PTX versus each combination chemotherapy with S-1 in patients with advanced gastric cancer refractory to S-1 or S-1 plus CDDP.

4064 Background: S-1 plus cisplatin (SP) is recognized as standard first-line chemotherapy for advanced gastric cancer (AGC) and S-1 monotherapy is recognized as standard adjuvant chemotherapy for ...

Influence of Socioeconomic Status on Survival and Clinical Outcomes in Patients with Advanced Gastric Cancer after Chemotherapy

Background: Socioeconomic inequalities are known to influence the survival of cancer patients due to differences in treatment modalities and disease extent at diagnosis. However, there are few studies regarding the influence of socioeconomic status on patient survival, especially after palliative chemotherapy for advanced gastric cancer. Patients and Methods: This retrospective study was performed on 138 advanced gastric cancer patients who received palliative chemotherapy. Demographic, socioeconomic, and cancer-related variables were analyzed according to education level. Effects of socioeconomic factors and cancer-related variables on patient survival were also evaluated. Results: In our study, higher education level (> 6 years of schooling; p = 0.01), disease control (p < 0.01), and a greater number of chemotherapeutic agents (≥ 5 drugs; p < 0.01) were associated with a significant increase in median survival. Multivariate analysis showed that a higher education level (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.35-0.82; p < 0.01), disease control (HR 0.21; 95% CI 0.13-0.34), and total number of chemotherapeutic agents used (HR 0.44; 95% CI 0.26-0.73) were significantly associated with prolonged survival. Conclusions: Among socioeconomic factors, only higher education level was associated with better survival. Increase in survival was also associated with clinical outcomes, including total number of chemotherapeutic agents used and disease control after chemotherapy.

Gastric cancer: toward a cisplatin-free disease?

Historically, the cornerstone of treatment of advanced gastric cancer (GC) is 5-fluorouracil (5-FU)-based chemotherapy that increases median overall survival (OS) compared to best supportive care by some months. The addition of cisplatin (CDDP) to chemotherapy doublets showed a limited but significant benefit in term of OS according to a Cochrane meta-analysis. However, the recent individual patient-data GASTRIC meta-analysis, confirms this benefit in term of progression-free survival (PFS) but not OS, in randomized eight trials that include or not CDDP. The substitution of CDDP with a modern agent (oxaliplatin, irinotecan or taxanes) has been poorly evaluated in the literature. The REAL-2 phase III trial confirmed the equivalence of oxaliplatin and CDDP-based triplets, and a meta-analysis of three oxaliplatin-based randomized trials demonstrated that these combinations are better that CDDP-based doublets or triplets, improving both PFS (HR =0.88) and OS (HR =0.88). In particular, oxaliplatin-based chemotherapy was associated with less neutropenia and thromboembolic events, but with worse neurotoxicity. Given that the role of chemotherapy in advanced GC is palliative, CDDP-free regimens, and in particular oxaliplatin-based chemotherapy, may be considered for both CDDP-fit and unfit patients (that are those with poor renal function, older age, bad performance status or who cannot tolerate forced hydration for example). The limited absolute survival benefit of chemotherapy in advanced GC (few weeks at best), the cumbersome vascular toxicity of CDDP and the activity of several new drugs such irinotecan, oxaliplatin, taxanes and oral fluoropyrimidines make nowadays possible to consider CDDP-free regimens for the treatment of this incurable disease.

Correction: Change of Body Weight and Macrophage Inhibitory Cytokine-1 during Chemotherapy in Advanced Gastric Cancer: What Is Their Clinical Significance?

Correction: Change of Body Weight and Macrophage Inhibitory Cytokine-1 during Chemotherapy in Advanced Gastric Cancer: What Is Their Clinical Significance?

An Updated Meta-Analysis of Randomized Controlled Trial Assessing the Effect of Neoadjuvant Chemotherapy in Advanced Gastric Cancer

Patients with locally advanced gastric cancer (AGC) have a poor outcome. We performed an updated meta-analysis to assess the effect of neoadjuvant chemotherapy (NAC). By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC combined surgery versus surgery alone in advanced gastric and gastroesophageal cancer would be included. All calculations and statistical tests were performed. Twelve RCTs with a total of 1,820 patients were included. All patients had resectable gastric or gastroesophageal cancer and received NAC. NAC can slightly improve the survival rate [OR = 1.32, 95% confidence interval (CI): 1.07–1.64, P = 0.01], little, or no significant benefits were suggested in subgroup analyses between different population and regimens either. It can significantly improved the 3-year progression-free survival (PFS) [OR: 1.85 (1.39, 2.46), p < .0001], tumor down-staging rate [OR: 1.71 (1.26, 2.33), p = .0006] and R0 resection rate [OR: 1.38 (1.08, 1.78) p = .01] of patients with AGC. There were no difference between the two arms, in terms of relapse rates [OR: 1.03 (0.60, 1.78), p = 0.92], operative complications [OR: 1.20 (0.90, 1.58), p = 0.21], perioperative mortality [OR: 1.14 (0.64, 2.05), p = 0.65], and grade 3/4 adverse effects. NAC can significantly down-stage the tumor and improve R0 resection rate of patients with gastric and gastroesophageal cancer. It is safe and feasible, and can be tolerated. NAC can slightly improve the survival rate. It needs further prospective multinational multicenter RCTs to define the clinical benefits of NAC and the most effective strategies for gastric and gastroesophageal cancer.

Association between Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in advanced gastric cancer: a Meta-analysis

Objective To quantitatively evaluate the association between Ile105Val polymorphism of glutathione S-transferase pi (GSTP1) and sensitivity to platinum-based chemotherapy in advanced gastric cancer.Methods The relevant published literatures about Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in gastric cancer were retrieved from China National Knowledge Internet (CNKI),VIP,Chinese Biomedical Literature Data (CBM),Wan-Fang databases,PubMed,EMBASE and Cochrane Library.Clinical response (complete response and partial response) was employed to estimate chemosensitivity.Meta-analysis was conducted by the RevMan 5.2 software,odds ratio (OR) with 95％ confidence interval (CI) were calculated.Publication bias was identified using Stata 12.0 software.Results A total of 724 cases from 6 case-control trials were included.The results of Meta-analysis showed the different statistical significance was found between GSTP1 Ilel05Val polymorphism and clinical response in the follow genotypes [GG+GA vs AA:OR =2.38,95％CI (1.29 ～4.38); GG vs GA + AA:OR =3.66,95％CI (1.18 ～11.39) ; GG vs AA:OR =4.42,95％ CI (1.28 ～ 15.26)] and Asian population subgroups [GG + GAvs AA:OR =2.93,95％ CI (1.33 ～ 6.48)].Conclusion Polymorphism of GSTP1 Ile105Val(A/G) may be associated with platinum-based chemosensitivity in advanced gastric cancer. Key words: Stomach neoplasms ; Drug therapy; Polymorphism, single nucleotide ; Meta-analysis ; Glutathione S-transferase pi

Quality of life in patients with advanced gastric cancer sequentially treated with docetaxel and irinotecan with 5-fluorouracil and folinic acid (leucovin)

With a median overall survival of only 9-13 months in patients with advanced gastric cancer (GC), the quality of life (QoL) during the palliative treatment remains a key issue. Furthermore, when combinations of two or three drugs are used, the impact on QoL should be carefully evaluated. This was studied within the GATAC trial in patients sequentially treated with docetaxel and irinotecan with 5-fluorouracil and leucovorin (5-Fu/Lv). Patients with previously untreated advanced GC were randomly assigned to start with docetaxel 45 mg/m(2) (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus and 44 h infusion of 5-Fu/Lv (D1, q2 weeks). After four courses, there was a prescheduled crossover to the alternative regimen for four additional courses. QoL was measured with the EORTC QLQ-C30 questionnaire at the start of the treatment, at crossover and after completing treatment with both regimens. Eighty-one patients were randomized, and 78 patients started treatment. A total of 191 completed QoL questionnaires were collected. There were no statistically significant differences in QoL scores between the two treatment groups and no changes in mean scores during the 16 weeks of treatment. During the last 8 weeks of treatment, a significantly larger portion of patients with radiological response reported sustained or better QoL scores than those with no radiological response (82 vs. 50%, p = 0.007). Chemotherapy in advanced GC did not affect QoL average scores. Patients with non-responding tumours reported more often a decline in the global QoL score. The concept of the pre-scheduled switch of chemotherapy regimens prior to progression should be further studied in this disease, as it appears effective, tolerable and not to negatively affect QoL.

Efficacies of neoadjuvant chemotherapy plus nutritional support in advanced gastric cancer complicated with pylori obstruction

To explore the efficacies of neoadjuvant chemotherapy plus nutritional supports for gastric cancer complicated with pyloric obstruction. Retrospective analyses were performed for a total of 116 patients of gastric cancer complicated with pyloric obstruction undergoing exploratory laparotomy from January 2004 to June 2013. Sixty-two patients (group A) received neoadjuvant chemotherapy (regimen of FOLFOX) plus preoperative nutritional support. And parenteral (PN, n = 30) and enteral (EN, n = 32) nutritional supports were provided. Another 54 patients (group B) underwent exploratory laparotomy alone. The serum level of albumin and score of quality of life in group A at the last preoperative day improved significantly. And EN was better than PN. The rate of excision/radical excision of group A (85.5%, 45.2%) was much higher than group B (64.8%, 18.5%) (both P < 0.05). Nutritional support, especially EN, can improve the nutritional status and quality of life in patients with gastric cancer complicated with pyloric obstruction. And nutritional support plus neoadjuvant chemotherapy increase the rate of tumor excision.

Change of Body Weight and Macrophage Inhibitory Cytokine-1 during Chemotherapy in Advanced Gastric Cancer: What Is Their Clinical Significance?

BackgroundWeight loss in advanced gastric cancer (GC) has been widely acknowledged to be a predictor for poor survival. However, very few studies have investigated the weight loss that occurs during chemotherapy. Therefore, we focused on weight loss during chemotherapy in patients with advanced GC and investigated the concentrations of macrophage inhibitory cytokine-1 (MIC-1), which has been recognized as a probable etiological factor in anorexia and weight loss.MethodsWe analyzed 384 patients with inoperable locally advanced or metastatic GC receiving first-line chemotherapy. Patients were assigned to one of two groups on the basis of their weight change during chemotherapy: >3% weight loss and ≤3% weight loss. Serum MIC-1 and C-reactive protein (CRP) concentrations were also assessed in these patients.ResultsThe >3% weight loss group had shorter overall survival (OS; 12.0 months vs. 17.5 months, P = 0.000) than the ≤3% weight loss group, and the survival rates improved if the weight loss was reversed during chemotherapy. Although the MIC-1 concentrations were not correlated with weight loss before (P = 0.156) or during chemotherapy (P = 0.164), it correlated significantly with the CRP concentration (P = 0.001). Furthermore, elevated MIC-1 concentrations before chemotherapy (P = 0.017) and increased MIC-1 concentrations during chemotherapy (P = 0.001) were both found to be predictors of poor OS.ConclusionsChanges in the body weight during chemotherapy could influence the prognosis in patients with advanced GC, and the MIC-1 might be a potential predictive and prognostic biomarker in those patients.

RETRACTED: Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of randomized controlled trials

To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC). By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software. 12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39-2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08-1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60-1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90-1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64-2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25-1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41-1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27-5.93, p = 0.76). NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.

Efficacy of intraperitoneal and intravenous chemotherapy for advanced gastric cancer with peritoneal metastasis.

Peritoneal metastasis (PM) in patients with advanced gastric cancer (AGC) is a poor prognostic indicator. The aim of this study was to compare the response of AGC patients with PM to paclitaxel-based systemic multidrug chemotherapy with and without additional intraperitoneal (IP) chemotherapy through retrospective analysis. Two hundred and sixty-three AGC patients with PM were enrolled. Eighty-two patients received systemic paclitaxel/oxaliplatin and leucovorin/5-fluorouracil (POF) and 181 patients received 2-drug systemic therapies, PO (paclitaxel + oxaliplatin) or PF (paclitaxel + 5-fluorouracil + leucovorin), and IP infusion of a third drug. Patients who received the POF regimen had longer progression-free survival (PFS) and overall survival (OS) than patients who received PO/PF + IP therapy (P = 0.026 and P = 0.046), respectively. In subgroup analysis, no significant differences in PFS and OS were observed between the POF regimen and PF/PO + IP regimens in patients with isolated peritoneal metastatic disease. Patients with multiorgan metastatic disease receiving POF had better PFS and better OS than patients receiving PO/PF + IP chemotherapy (P = 0.005 and P = 0.036, respectively). In multivariate analysis, ECOG performance status and the interaction between different therapeutic strategies and multiorgan metastasis were independent prognostic factors for survival. Leukopenia, fatigue and peripheral neuropathy were higher on the triplet regimen than the doublet regimens. Paclitaxel-based doublet therapy combined with IP chemotherapy had more manageable toxicity and equal efficiency compared to triplet therapy for AGC patients with isolated PM. The POF regimen may be a good choice for AGC patients with multiorgan metastasis, especially those having a good performance status.

Evaluation of usefulness of Royal Marsden Hospital prognostic index in second-line chemotherapy of advanced gastric cancer.

163 Background: Royal Marsden Hospital prognostic Index (RMH-I), which was based on performance status, ALP, liver metastasis and peritoneal metastasis, was reported as prognostic factor of advanced esophago-gastric cancer before first line chemotherapy (Chau I, et al. J Clin Oncol 22:2395-2403, 2004). Usefulness of RMH-I in second line chemotherapy is not elucidated. Methods: Advanced gastric cancer patients who started second line chemotherapy in Hokkaido University Hospital from July 2001 to May 2013 with prior fluoropyrimidine plus platinum administration were retrospectively analyzed. Univariate and multivariate analysis for overall survival were performed using patient characteristics (RMH-I, hemoglobin, CRP, CEA, Alb, TTP in first line, primary lesion resection, and bone metastasis). Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 77 eligible patients. Male/Female were 52/25, median age was 60 years (range 31-80) and unresectable/recurrent were 70/7. Median survival was 7.1 months. The distribution and median survival for RMH-I groups were as follows: good risk (n = 8), 8.2 months; moderate risk (n = 57), 9.6 months; and poor risk (n = 12), 4.4 months. Although poor risk group showed shorter survival time, there were not significant difference regardless of RMH-I in Cox multivariate analysis (HR 1.12, 95%CI 0.61-2.09, P=0.72). Conclusions: In this retrospective analysis, RMH-I was not independent prognostic factor in second line chemotherapy of advanced gastric cancer. Prognostic factors in this population need to be investigated further.

Potential predictive markers of chemotherapy for advanced gastric cancer: Biomarker study in GC0301/TOP-002, randomized phase III study of irinotecan plus S-1 versus S-1.

55 Background: Irinotecan plus S-1(IRI-S) achieved longer median survival than S-1 monotherapy and was well tolerated for patients with advanced gastric cancer (AGC) in GC0301/TOP-002, but it did not show significant superiority (Gastric Cancer 2011). According to subset analyses, IRI-S may have extra survival benefit in some group of patients, prompting to explore prognostic or predictive markers.We correlated expression of 5 genes related to DNA and anticancer drug metabolism (TS, DPD, Topo-I, ERCC1, TP) with outcome of patients in each arm. Methods: Paraffin-embedded primary tumor specimens before chemotherapy were available from 126 of 326 patients. mRNA expression in microdissected tumors was measured by real-time RT-PCR, and categorized into low and high using the median as a cut-off. Multivariate analysis for overall survival (OS) adjusting baseline factors, gene expression and treatment (S-1/IRI-S) was performed with a Cox regression model. Interaction tests were also carried out between gene expression and treatment. Results: Although baseline factors of the subjects were similar to the entire GC0301/TOP-002 trial, median survival seemed opposite; 13.1M for S-1 and 11.4M for IRI-S arm, p=0.192. 92 samples, 47 of S-1 and 50 of IRI-S arm, were assessable for 5 genes. Multivariate analyses showed that liver metastasis correlated with poor prognosis (HR, 2.73; 95% CI, 1.50-5.01; P=0.011), but no gene was significantly correlated with OS. There were interactions between the treatment effect for DPD and TP. HRs between high and low DPD were 3.02 in S-1 and 0.96 in IRI-S arm, p=0.012 for interaction; while those for TP were 2.98 in S-1 and 0.38 for IRI-S arm, p=0.002. In patients with low TS and high Topo-I (n=18), OS was 11.2M for S-1 and 18.6M for IRI-S arm, p=0.531. Conclusions: The correlative analyses suggest DPD and TP are predictive factor for the first-line treatment of AGC including S-1 and irinotecan. Combined biomarker analyses with the previous randomized phase III study including S-1 or irinotecan is warranted to verify these findings.

Randomized, multicenter, controlled evaluation of S-1 and oxaliplatin (SOX regimen) as neoadjuvant chemotherapy for advanced gastric cancer patients (RESONANCE trial).

90 Background: RESONANCE trial aims to improve 3-year disease-free survival (DFS) for patients treated with neoadjuvant chemotherapy and D2 surgery with chemotherapy postoperatively. We also evaluated the postoperative complications with and without preoperative chemotherapy to reveal the safety of SOX regimen. Methods: In this phase III multicenter study, patients with American Joint Committee on Cancer(AJCC,7thed)stage II-IIII advanced gastric cancer are treated with two to four cycles of preoperative SOX chemotherapy, followed by gastrectomy with D2 lymphadenectomy, and then another four to six postoperative cycles of SOX chemotherapy. Surgical and pathological quality control is performed. The primary endpoint is 3-year DFS, secondary endpoints are 3-year OS, D2/R0 rate, and toxicity and recurrence risk. The RESONANCE trial has been registered internationally, and twenty hospitals have participated in this trial. Results: Between February 2012 and to August 2013, 128 patients were enrolled in the neoadjuvant group , 103 patients were enrolled in the adjuvant group. Seventy-four of 128 patients underwent gastrectomy with D2 lymphadenectomy after preoperative chemotherapy. In these 74 patients, 52 (70%) patients had clinical tumor response and 10 (14%) patients achieved histological response. Operative mortality was never encountered. R0 resection rate was 90.5% after neoadjuvant chemotherapy compared with 94.2% in adjuvant group (p=0.23). Postoperative complication rates in neoadjuvant and adjuvant groups were 33.8% and 37.9% respectively (p=0.58). Conclusions: Results of this study will demonstrate whether neoadjuvant chemotherapy strategy will be superior to adjuvant chemotherapy when combined with D2 surgery for AJCC stage II-III gastric cancer patients. Furthermore, it might be an important clinical evidence to verify benefit of neoadjuvant chemotherapy in advanced gastric cancer. Clinical trial information: NCT01583361.