Unresectable Advanced Gastric Cancer Research Articles

Treatment features of systemic chemotherapy in young adults with unresectable advanced or recurrent gastric cancer

PurposeGastric cancer in young adults (GCYA) is known to have distinct clinicopathological features, including a female predominance and diffuse-type histology. Previous reports have focused on patients who had undergone gastrectomy with curative intent. Information concerning the treatment of unresectable advanced- or recurrent-stage GCYA is lacking. Therefore, we aimed to investigate whether the distinct clinicopathological features of GCYA affect the outcome of systemic chemotherapy.Patients and methodsWe conducted a retrospective cohort study at a single institution in Japan. GCYA was classified as a disease in individuals who were <40 years of age at diagnosis. Initial systemic chemotherapy regimens for GCYA were investigated with a focus on patients who received S-1 plus cisplatin (SP) as a representative standard regimen. The efficacy, safety, and feasibility of systemic chemotherapy were evaluated.ResultsEighty-nine (7.5%) of 1,184 consecutive patients who received systemic chemotherapy at our institute between December 2005 and June 2016 were enrolled. As reported previously, the female sex (57.3%) and diffuse-type histology (91.0%) were the dominant features of GCYA. Thirty-two patients (36.0%) received SP as first-line treatment. The median overall survival and progression-free survival times were 13.2 (95.0% CI: 9.5–18.7) and 5.6 (95.0% CI: 4.7–7.9) months, respectively. The median number of treatment cycles, relative dose intensity, and cumulative dose of cisplatin were 4.5 (range: 1–10), 92.0% (IQR: 83.5–98.3), and 286.5 mg/m2 (IQR: 172.5–367.5), respectively. The most common adverse event of Grade 3 or higher was neutropenia (n=5 patients; 15.6%). No patient had febrile neutropenia. Non-hematological adverse events of Grade 3 or higher were only observed in 2 (6.3%) of 32 patients.ConclusionStandard chemotherapy used for general-aged GC patients has similar efficacy, reduced toxicity, and higher intensity in GCYA patients.

Clinical efficacy of immune checkpoint inhibitors in the treatment of unresectable advanced or recurrent gastric cancer: an evidence-based review of therapies.

Standard treatment options for patients with advanced gastric cancer (GC) offer limited efficacy and are associated with some toxicity, which necessitates the development of more effective therapies for improving the treatment outcomes for this disease. Immunotherapy involving immune checkpoint inhibitors (ICIs) which inhibit the programmed death 1 (PD-1)/programmed death ligand 1 interaction has emerged as a new treatment option. Nivolumab, a human IgG4 monoclonal antibody inhibitor of PD-1, has demonstrated promising clinical activity and induced durable responses in patients with advanced GC. Nivolumab has recently been approved for treating patients with pretreated advanced GC in Japan. In the present review, we summarized current evidence of the clinical efficacy of ICIs in a variety of solid tumors and reported our experience in patients with GC who were treated with nivolumab and the interesting features that were observed in these cases. Certain ICI-specific clinical features such as pseudo- and hyper-progression of tumor and hyper-response to subsequent chemotherapy have been reported in several cancer types. Lastly, we discussed the present scenario regarding research on biomarkers for assessing the clinical benefits of ICI therapies.

Abstract CT147: Safety and efficacy of high purity and activity NK cells therapy in combination with IgG1 antibody in patients with gastric or colorectal cancer: A phase I clinical trial

Abstract Background; Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells, and produce numerous cytokines resulting in the activation of the adoptive immune systems. Thus, NK cell is considered ideal cell for adoptive cancer immunotherapy. But the difficulty of obtaining large numbers of NK cells that are safe to administer deters its clinical use. We successfully generated large numbers of activated NK cells from small quantities of blood and also determined that the expanded cells were safe to administer in a monotherapy (J Transl Med (2015) 13:277). Since NK cells play a key role in antibody-dependent cellular cytotoxicity (ADCC), administration of NK cells would be expected to enhance the efficacy of IgG1 monoclonal antibodies by augmenting ADCC. This phase I clinical trial evaluated the safety, toxicity, and immunological response of the adoptive NK therapy in combination with IgG1 antibodies. Patients and Methods; Patients with unresectable advanced gastric or colorectal cancer who have administered or have planned to administer IgG1 antibody (i.e. trastuzumab for HER2 positive gastric cancer or cetuximab for RAS-wild colorectal cancer). NK cells were expanded from PBMCs with the same method in previous clinical trial, briefly ex vivo by stimulating PBMCs with OK432, IL-2, and modified FN-CH296-induced T cells. Expanded NK cells were intravenously injected 3 days after IgG1 antibody administration in a dose-escalating manner (dose 0.5 × 109, 1.0 × 109, 2.0 × 109 cells/injection, three patients/one cohort), every 3 weeks for 3 cycles. We evaluated the safety and efficacy of the combination therapy. To assess the immunological response, immunomonitoring was performed. Results; Nine eligible patients were enrolled. NK cell populations expanded with our system were confirmed as being enriched in NK cells (median 92.9%) with high expression of NKG2D(97.6%) and CD16(69.6%). This combination therapy was well tolerated with no severe adverse events. Among six evaluable patients, 4 presented SD, 2 presented PD. Of the four SD patients, 3 showed an overall decrease in tumor size after combination therapy. In immunomonitoring analysis, whole blood IFN-gamma production level was increased and the proportion of Treg (Treg/CD4) in peripheral blood was decreased after the combination therapy. Conclusions; This is the first clinical trial of the combination of adoptive NK cell therapy and IgG1 monoclonal antibodies. Our data provide evidence of good tolerability and preliminary anti-tumor activity for this combination therapy. Moreover, immunological monitoring revealed that the combination therapy induced Th1-type immune response and reduced peripheral Tregs. However, given the limited activity observed in this clinical trial, additional studies are necessary to develop these combination approaches. Citation Format: Takeshi Ishikawa, Tetsuya Okayama, Naoyuki Sakamoto, Mitsuko Ideno, Kaname Oka, Tatsuji Enoki, Junichi Mineno, Hideyuki Konishi, Satoshi Kokura, Yuji Naito, Yoshito Itoh. Safety and efficacy of high purity and activity NK cells therapy in combination with IgG1 antibody in patients with gastric or colorectal cancer: A phase I clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT147.

The association of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) expression with gastric cancer prognosis.

Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor. Untreated peripheral blood specimens were obtained from 111 patients with gastric cancer and 20 healthy volunteers. HHLA2 mRNA expression levels were determined using quantitative RT-PCR assay. Blood specimens obtained from patients with gastric cancer had significantly lower copies of HHLA2 mRNA than those obtained from healthy volunteers (P < 0.0001). Furthermore, HHLA2 expression was significantly correlated with the depth of tumor invasion (P = 0.0331), distant metastasis (P < 0.0001), and stage of disease (P = 0.0032). The 5-year survival rate was significantly higher in patients with high HHLA2 expression compared with the patients with low expression (P = 0.0001). These findings demonstrate that assessment of HHLA2 expression levels in the blood could be utilized to predict tumor aggressiveness in patients with gastric cancer.

Retrospective observational study of salvage line ramucirumab monotherapy (RAM) for patients (pts) with unresectable advanced gastric cancer (AGC) which was refractory to fluoropyrimidine and taxanes.

129 Background: RAM showed a survival benefit over best supportive care in second-line treatment after failure of fluoropyrimidine-containing chemotherapy for pts with advanced gastric or gastro-esophageal junction adenocarcinoma (AGC). In clinical practice, RAM is used for some pts who have disease refractory to fluoropyrimidine and taxanes in salvage line setting. Methods: We retrospectively evaluated efficacy and safety of RAM in salvage lines between June 2015 and April 2017 for AGC at four Japanese institutions. All pts received 2 or more prior regimens containing fluoropyrimidine and taxanes, but not ramucirumab. We also explored prognostic factors for progression free survival (PFS) and overall survival (OS). Results: Fifty-one pts were collected. Pts' characteristics were as follows; median age: 67 (range 39-84) years; ECOG performance status ≤ 1: 43 (84%) pts; HER2 positive: 17 (33%) pts; number of metastatic sites ≥ 2: 29 (57%); number of prior therapies 2/3/4/5: 7(14%)/25(49%)/12(24%)/7(14%) pts. Median PFS and OS were 1.9 (95% confidence interval [CI]: 1.6-2.2) and 5.1 (95% CI: 4.1-6.8) months, respectively. Twelve-week PFS rate was 25.5%. Objective response rate in 43 pts who had measurable disease was 2%. Disease control rate was 35%. Grade 3 adverse events (AEs) occurred in 7 (13%) pts such as anemia in 2 (4%), fatigue in 1 (2%), hypertension in 2 (4%), proteinuria in 2 (4%), intestinal bleeding in 1 (2%), and others in 2 (4%) pts. No grade 4 AEs and treatment related deaths were observed. Although multivariate analyses suggested that absence of primary tumor and neutrophil lymphocyte ratio &lt; 2.5 at baseline were associated with better PFS, while statistically significant prognostic factors for OS were not identified in this study. Conclusions: Salvage line RAM showed acceptable toxicities and comparable efficacy with those reported in previous studies of second-line setting. It is suggested that RAM could be considered for salvage line treatment after fluoropyrimidine and taxanes containing regimens.

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer

BackgroundNanoparticle albumin-bound (nab)-paclitaxel was developed to improve paclitaxel solubility and does not need premedication to avoid infusion-related reactions associated with solvent-based (sb)-paclitaxel. We conducted a phase II trial to investigate the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer. Patients and methodsPatients with unresectable advanced gastric cancer refractory to first-line chemotherapy were administered nab-paclitaxel 100 mg/m2 intravenously on days 1, 8 and 15, plus ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary end-point was Independent Review Committee (IRC)–assessed overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and quality of life (QOL). ResultsForty-five patients were enrolled; 43 received the study treatment. The ORR assessed by the IRC was 54.8% (90% confidence interval [CI] 41.0–68.0) and the primary end-point was met. The DCR was 92.9% (95% CI 80.5–98.5). The IRC-assessed median PFS was 7.6 months (95% CI 5.4–8.1). The median OS was not reached at the data cutoff. The main treatment-related grade 3 or 4 adverse events were decreased neutrophil count (76.7%), decreased white blood cell count (27.9%), anaemia (11.6%), decreased appetite (7.0%), febrile neutropenia (4.7%), hypertension (4.7%) and proteinuria (4.7%). No treatment-related deaths occurred. No QOL deterioration was observed during study treatment. ConclusionNab-paclitaxel plus ramucirumab combination therapy shows promising activity and manageable toxicities and could be a useful second-line treatment option for patients with previously treated advanced gastric cancer.

Serum carbohydrate antigen 125 is a significant prognostic marker in patients with unresectable advanced or recurrent gastric cancer.

We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer. The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients. The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5months, which was significantly shorter than that of a normal range group (18.3months, P<0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P<0.001). Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival.

Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial

Patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, two or more previous regimens of chemotherapy have a poor prognosis, and current guidelines do not recommend any specific treatments for these patients. We assessed the efficacy and safety of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), in patients with advanced gastric or gastro-oesophageal junction cancer who had been previously been treated with two or more chemotherapy regimens. In this randomised, double-blind, placebo-controlled, phase 3 trial done at 49 clinical sites in Japan, South Korea, and Taiwan, eligible patients (aged ≥20 years with unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, standard therapy [including two or more previous chemotherapy regimens], with an Eastern Cooperative Oncology Group [ECOG] performance status of 0-1, and naive to anti-PD-1 therapy or other therapeutic antibodies and pharmacotherapies for the regulation of T cells) were recruited. Patients were randomly assigned (2:1) using an interactive web response system to receive 3 mg/kg nivolumab or placebo intravenously every 2 weeks, stratified by country, ECOG performance status, and number of organs with metastases. Study treatment was continued until progressive disease per investigator assessment or onset of toxicities requiring permanent discontinuation. Patients and investigators were masked to group assignment. The primary endpoint was overall survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study treatment. This study is ongoing but not recruiting new patients, and is registered with ClinicalTrials.gov, number NCT02267343. Between Nov 4, 2014, and Feb 26, 2016, we randomly assigned 493 patients to receive nivolumab (n=330) or placebo (n=163). At the data cutoff (Aug 13, 2016), median follow-up in surviving patients was 8·87 months (IQR 6·57-12·37) in the nivolumab group and 8·59 months (5·65-11·37) in the placebo group. Median overall survival was 5·26 months (95% CI 4·60-6·37) in the nivolumab group and 4·14 months (3·42-4·86) in the placebo group (hazard ratio 0·63, 95% CI 0·51-0·78; p<0·0001). 12-month overall survival rates were 26·2% (95% CI 20·7-32·0) with nivolumab and 10·9% (6·2-17·0) with placebo. Grade 3 or 4 treatment-related adverse events occurred in 34 (10%) of 330 patients who received nivolumab and seven (4%) of 161 patients who received placebo; treatment-related adverse events led to death in five (2%) of 330 patients in the nivolumab group and two (1%) of 161 patients in the placebo group. No new safety signals were observed. In this phase 3 study, the survival benefits indicate that nivolumab might be a new treatment option for heavily pretreated patients with advanced gastric or gastro-oesophageal junction cancer. Ongoing trials that include non-Asian patients are investigating nivolumab for advanced gastric or gastro-oesophageal junction cancer in various settings and earlier treatment lines. Ono Pharmaceutical and Bristol-Myers Squibb.

Computed tomographic characteristics for patients with unresectable gastric cancer harboring low-volume peritoneal carcinomatosis.

Although current staging workups could differentiate most patients with operable from inoperable advanced gastric cancers, there are still some patients with low-volume peritoneal carcinomatosis, defined as only metastasis with multiple subcentimeter lesions in peritoneum, receiving unnecessary open-close procedures. The computed tomography (CT) of the patients with unresectable advanced gastric cancer harboring low-volume peritoneal carcinomatosis was retrospectively identified and then thoroughly reviewed by two independent radiologists unaware of the peritoneal carcinomatosis status. Of the 798 patients with newly diagnosed gastric cancer between January 2007 and December 2010, 52 patients harboring advanced gastric cancer with low-volume peritoneal carcinomatosis receiving surgery with curative intent were identified. Descriptive statistic was used for the radiologic characteristics. The most common radiologic characteristic of CT was omental fat stranding (57.7%), followed by omental clustered subcentimeter nodules (53.8%), distant enlarged lymph node (40.4%), distant grouping of small lymph nodes (36.5%), peritoneal nodules or thickening (34.6%), minimal loculated ascites (21.2%), intestinal wall thickening or irregularity (9.6%), and hydronephrosis or hydroureter without stone or urothelial lesion (5.8%). Comprehensively reviewing the radiologic characteristics of CT may identify the patients harboring advanced gastric cancer with low-volume peritoneal carcinomatosis.

Clinical efficacy of neoadjuvant chemotherapy regimens FLEEOX vs. XELOX in patients with initially unresectable advanced gastric cancer: a propensity score analysis.

PurposeThis study was designed to assess the effectiveness of FLEEOX (5-Fu, leucovorin, etoposide, oxaliplatin, and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as neoadjuvant chemotherapy (NAC) for initially unresectable advanced gastric cancer (AGC).MethodsThis study reviewed patients who underwent FLEEOX or XELOX for initially unresectable AGC. To reduce the bias in patient selection, we conducted propensity score match (PSM) with 1:1 ratio. Tumor and pathological response, surgical characteristics, chemotherapy-related toxicity and overall survival (OS) were analyzed.ResultsFrom January 2004 to December 2012, 436 patients were enrolled; 99 pairs of patients were generated after PSM. The tumor response rates were 80.8% and 68.7% in FLEEOX and XELOX (P=0.018). 80 patients (80.8%) in FLEEOX and 63 (63.6%) in XELOX received radical resection (P<0.001). The pathological complete response rate and R0 rate were 11.1% and 69.7% in FLEEOX, respectively, while 4.8% and 38.4% in XELOX (P<0.001). Median OS time was longer in FLEEOX (30.0 vs. 25.1 months, P<0.001). In addition, more toxicities occurred in FLEEOX, including leukocytopenia (17.2% vs. 7.1%, P=0.024), nausea (17.2% vs. 6.1%, P=0.012) and vomiting (22.2% vs. 10.1%, P=0.016). The overall toxicity rate was higher in FLEEOX (71.7% vs. 35.4%, P<0.001).ConclusionThe FLEEOX regimen as NAC for patients with initially unresectable AGC can improve tumor response rate, radical resection rate, R0 rate, and OS as compared to XELOX regimen. More chemotherapy-related toxicity was observed in FLEEOX group, although no chemotherapy-related deaths and aborting were observed. Further randomized clinical trials on the FLEEOX regimen are necessary.

Sa1273 - Ratio of Neutrophil to Lymphocytes is Useful to Predict the Prognosis of Patients with Paclitaxel Plus Ramucirumab Treatment for Unresectable Advanced Gastric Cancer

Sa1273 - Ratio of Neutrophil to Lymphocytes is Useful to Predict the Prognosis of Patients with Paclitaxel Plus Ramucirumab Treatment for Unresectable Advanced Gastric Cancer

Phase II study of S-1 plus docetaxel as first-line treatment for elderly patients with advanced gastric cancer (OGSG0902).

129 Background: There is not enough evidence for the treatment of elderly patients with advanced gastric cancer. S-1 plus CDDP is one of the standard treatment for advanced gastric cancer in japan, but the efficacy remains insufficient due to the drug toxicity such as renal function disorders. The efficacy and safety of S-1 plus docetaxel as first-line treatment for elderly patients with unresectable advanced or recurrent gastric cancer were investigated. Methods: 75 years or older patients with unresectable advanced or recurrent gastric cancer were enrolled. Docetaxel was administered i.v. (40mg/m2) on day 1, while S-1 was administered orally (80mg/m2/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks. The primary endpoint was response rate (RR) of S-1 plus docetaxel; secondary endpoints were safety, progression free survival (PFS), time to treatment failure (TTF) and overall survival (OS). Sample size was set to be 30, which was determined to reject the response rate of 20% under the expectation of 40% with the power of 90% and two-sided alpha of 5%. Results: 31 patients were enrolled and assessable for efficacy. The response rate was 45.2% (95%CI 27.3-64.0, p = 0.001), and disease control rate was 77.4%. The median progression-free survival time was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1months. In 31 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for elderly patients is feasible and shows promising efficacy against advanced gastric cancer. Clinical trial information: UMIN000002785.

Analysis of Factors Influencing the Tolerability of S-1 plus Oxaliplatin in Patients with Advanced Gastric Cancer

Oxaliplatin (L-OHP) was approved for the treatment of gastric cancer in 2015 in Japan. Cisplatin (CDDP) and L-OHP are used as the first-line therapy for unresectable advanced or recurrent gastric cancer. Compared with CDDP, L-OHP has fewer adverse effects such as nausea and vomiting. Moreover, L-OHP does not need a large amount of hydration. Many outpatients with gastric cancer can use L-OHP. L-OHP is used with S-1 (SOX) for unresectable advanced or recurrent gastric cancer. However, some patients need to take a reduced dose or discontinue therapy. Thus, we evaluated the factors that influence the tolerance to SOX, to improve treatment safety and predict adverse events. The study included 22 patients who were treated with SOX. Intolerant patients were defined as those who required a reduced dose or discontinuation of therapy. Eight patients were defined as intolerant. The factors that influenced tolerance included surgical history of gastric cancer (P = 0.018), body mass index < 18.5 (P = 0.039), low neutrophil count (P = 0.039), low platelet count (P = 0.039), and high aspartate transaminase level (P = 0.036). All intolerant patients underwent surgery for gastric cancer. The duration from surgery to the initiation of SOX in intolerant patients was shorter than that for tolerant patients (P = 0.021). In conclusion, the factors that influence tolerance in patients receiving SOX were short duration from surgery to SOX, low body mass index, low neutrophil count, low platelet count and high aspartate transaminase level. Therefore, patients who have these factors require careful monitoring for adverse events.

Clinical Outcomes of Endoscopic Hemostasis for Bleeding in Patients with Unresectable Advanced Gastric Cancer.

PurposeBleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC.Materials and MethodsThis study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated.ResultsSuccessful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ≥5 units of RBCs was a significant risk factor for rebleeding.ConclusionsDespite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (≥5 units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.

Multiple Lines of Chemotherapy for Unresectable Advanced or Recurrent Gastric Cancer

Multiple Lines of Chemotherapy for Unresectable Advanced or Recurrent Gastric Cancer

QT interval prolongation and torsades de pointes with oxaliplatin.

Oxaliplatin is a platinum-containing antineoplastic agent that is used in the treatment of gastrointestinal cancers [Stein and Arnold, 2012; Alcindor and Beauger, 2011]. It is one of the most important treatments for colorectal cancer, and is commonly used in combination therapy with other cytotoxic drugs [Stein and Arnold, 2012; Alcindor and Beauger, 2011]. It may have survival benefits and better tolerability than cisplatin for advanced unresectable gastric cancer [Montagnani et al. 2011]. Oxaliplatin may also be an alternative treatment for patients with ovarian cancer, who have shown hypersensitivity to carboplatin [Bogliolo et al. 2015].

Efficacy and safety of target combined chemotherapy in advanced gastric cancer: a meta-analysis and system review

BackgroundThe aim of our meta-analysis is to assess the efficacy and safety of the target combined chemotherapy for the patients with unresectable advanced or recurrent gastric cancer.MethodsIn accordance with the standard meta-analysis procedures, the patients included in our study were with unresectable advanced or recurrent gastric cancer and allocated randomly to receive target combined chemotherapy or the traditional chemotherapy. The search was applied to PubMed, EMBASE, Science Citation Index Expanded, Cocran’s library (from inception to February 2016). All analyses were performed by STATA 12.0, with the odds ratio, hazard ratio, and 95 % confidence interval as the effect measures.ResultsFourteen studies were included in this meta-analysis. A total of 5067 patients with advanced gastric cancer were divided into two arms: traditional chemotherapy arm and target combined chemotherapy arm. A significant improvement for overall survival (hazard ratio was 0.89, 95 % confidence interval: 0.83–0.95) and overall response rate (odds ratio was 1.44, 95 % confidence interval: 1.15–1.81) was observed, but no significant difference was found for progression-free survival (hazard ratio was 0.89, 95 % confidence interval: 0.77–1.00) in the target combined chemotherapy arm. In subgroup analysis, increasing benefits regarding overall survival and progression-free survival were found in anti epidermal growth factor receptor target drugs for selected patients subgroup and anti vascular endothelial growth factor receptor target drugs for unselected patients subgroup, but not in anti epidermal growth factor receptor target drugs for unselected patients subgroup. Besides, some adverse events were increased in the target combined chemotherapy arm.ConclusionsThe target combined chemotherapy represented a better overall survival benefit and treatment efficiency and higher incidence of some grade 3–4 adverse events than the traditional chemotherapy for patients with unresectable advanced or recurrence gastric cancer. The anti vascular endothelial growth factor receptor drugs can improve the efficacy in the whole patients with unresectable advanced or recurrence gastric cancer and the anti epidermal growth factor receptor target drugs can only improve the efficacy in the epidermal growth factor receptor positive patients.

Improvement of Chronic Bleeding in the Patient with Unresectable Advanced Gastric Cancer Using the Decoction of - a Case Report

Objectives: A 74-year-old male patient with unresectable advanced gastric cancer (clinical initial stage T3N+, Borrmann type III) admitted due to gastric bleeding at tumor site. On first admission day, hemoglobin level was 5.7g/dl and performance status was grade 3 according to Eastern Cooperative Oncology Group Performance Status(ECOG-PS). After performing red blood cell transfusion as an emergency treatment, hemoglobin level was increased up to 9.5g/dl. However, bleeding of oozing site was continued. For hemostasis, decoction of notoginseng radix (30g/day) was administered since day 7 after admission. The dose was elevated to 40g/day after hemoglobin level was decreased to 6.5g/dl on day 11. Since then, melena was stopped and hemoglobin level was maintained over 9.1g/dl. This case shows the hemostasis effect of decoction of notoginseng radix on gastric bleeding in unresectable advanced gastric cancer.

Evaluation of Systemic Inflammatory Response Biomarkers in Patients Receiving Chemotherapy for Unresectable and Recurrent Advanced Gastric Cancer

Background: The present study sought to evaluate an inflammation-based prognostic score (Glasgow prognostic score, GPS) and the neutrophil to lymphocyte ratio (NLR) as prognostic factors in patients receiving chemotherapy for advanced gastric cancer. Methods: The study enrolled 224 patients who received chemotherapy for advanced gastric cancer at the Kochi Medical School from 2007 to 2014. Clinicopathological information and systemic inflammatory response data were obtained to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median survival time was significantly higher for patients with intestinal-type compared to diffuse-type histology (p = 0.039), a GPS 0 score compared to GPS 1 or 2 score (p = 0.004), and lower compared to higher NLR 4 (p = 0.002). Multivariate survival analysis identified high NLR 4 (HR 1.651; 95% CI 1.187-2.297; p = 0.003) and diffuse-type histology (HR 1.645; 95% CI 1.025-2.639; p = 0.039) as significant independent predictors associated with worse prognosis in the studied group of cancer patients. Conclusions: NLR and histological type are independent prognostic factors for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer.

The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically.