Search

Background: In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m 2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m 2 (SOX130) in AGC., Methods: Patients with HER2-negative AGC received 80 mg/m 2 /day S-1 orally on days 1-14 and 130 mg/m 2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0., Results: Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%)., Conclusions: This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.

Purpose: This study aimed to evaluate cancer-related weight loss (WL) after the start of first-line chemotherapy as a surrogate marker for cancer cachexia in patients with advanced gastric cancer. We investigated the incidence of WL and the relationship between WL and overall survival (OS) or adverse events., Methods: We conducted a retrospective cohort study in 131 patients with advanced gastric cancer who received first-line systemic chemotherapy between September 1, 2010, and August 31, 2016, at Kurume University Hospital and Shizuoka Cancer Center Hospital. WL was defined in this study as weight loss of > 5% or weight loss of > 2% with a body mass index of < 20 kg/m 2 within the last 6 months after the start of chemotherapy., Results: Median age and median Eastern Cooperative Oncology Group performance status of the patients participating in this study were 68 years old and 0, respectively. Incidence of WL was 53% at the first 12 weeks after starting first-line chemotherapy, and increased to 88% after 48 weeks. Overall survival rates were significantly associated with WL at 12, 24, and 48 weeks. Appetite loss and fatigue were more frequent and more severe in patients with WL., Conclusion: WL was especially observed in more than half the patients within 12 weeks after starting chemotherapy. WL appeared to relate to adverse events or reduced survival. These results suggest the importance of monitoring WL or providing nutritional support at the beginning of chemotherapy.

We report a case of long-term survival in a 75-year-old male with advanced gastric cancer and Virchow's lymph node metastasis[cT3N3M1(LYM)H0P0, cStage Ⅳ]which received multidisciplinary treatment. Over 1 year and 6 months, 5 courses of S-1 plus CDDP, 14 courses of S-1 plus docetaxel, and 3 courses of S-1 plus CPT-11 were administered. Following chemotherapy, FDG-PET/CT showed FDG uptake only in the primary tumor and regional lymph nodes. Total gastrectomy and D2 dissection were performed. The pathological diagnosis was Type 5, 55×50 mm, L, Less, tub1>tub2, T3, int, INF b, ly2, v1, pPM0, pDM0, pN2(3/29), HER2(-). S-1 was used as adjuvant chemotherapy. Four years and 7 months after resection, cervical lymph node swelling was detected. The cervical lymph node was resected, followed by radiotherapy administration(56 Gy/28 Fr). No relapse occurred, and the patient has survived more than 7 years and 1 month and 8 years and 11 months after conversion surgery and diagnosis, respectively.

We aimed to investigate the impact of muscle atrophy and the neutrophil-to-lymphocyte ratio (NLR), a sub-clinical biomarker of inflammation and nutrition, on the prognosis of patients with unresectable advanced gastric cancer. We retrospectively enrolled 109 patients with stage IV gastric cancer (median age 69 years; female/male 22%/78%; median observational period 261 days). Independent factors and profiles for overall survival (OS) were determined by Cox regression analysis and decision-tree analysis, respectively. OS was calculated using the Kaplan-Meier method. The prevalence of muscle atrophy was 82.6% and the median NLR was 3.15. In Cox regression analysis, none of factors were identified as an independent factor for survival. The decision-tree analysis revealed that the most favorable prognostic profile was non-muscle atrophy (OS rate 36.8%). The most unfavorable prognostic profile was the combination of muscle atrophy and high NLR (OS rate 19.6%). The OS rate was significantly lower in patients with muscle atrophy and high NLR than in patients with non-muscle atrophy (1-year survival rate 28.5% vs. 54.7%; log-rank test p = 0.0014). In conclusion, "muscle atrophy and high NLR" was a prognostic profile for patients with stage IV gastric cancer. Thus, the assessment of muscle mass, subclinical inflammation, and malnutrition may be important for the management of patients with stage IV gastric cancer.

Background: RAS-RAF-MEK-ERK and PI3K-AKT pathways form a significant cascade for potential molecular target therapy in advanced cancer. The clinical significance of mutations in these genes in advanced gastric cancer (AGC) is uncertain., Methods: We collected formalin-fixed, paraffin-embedded and fresh frozen tumor samples from AGC patients and analyzed the KRAS, NRAS, BRAF and PIK3CA mutations by direct-sequencing. We retrospectively investigated the clinicopathological features of these mutations in AGC patients, and selected patients with metastatic gastric cancer., Results: Among 167 AGC patients, mutations of KRAS codons 12/13 (N = 8/164, 4.9%), PIK3CA (N = 9/163, 5.5%), and NRAS codon 12/13(N = 3/159, 1.9%) were detected. Comparison of the clinicopathological features of the mutated KRAS, PIK3CA, NRAS genes with an all-wild type of these genes showed that the frequency of the intestinal type was significantly higher in patients whose tumor tissue contained KRAS mutations (P = 0.014). Among 125 patients with metastatic gastric cancer, patients with NRAS codon 12/13 mutations in their tumors had shorter overall survival compared with NRAS wild-type patients (MST: 14.7 vs 8.8 months, P = 0.011). By multivariate analyses, NRAS codon 12/13 mutation was an indicator for poor prognosis in patients with metastatic gastric cancer (adjusted HR 5.607, 95% CI: 1.637-19.203)., Conclusions: Our study indicated that mutations of KRAS, PIK3CA and NRAS were rare in AGC. NRAS mutations were likely to associate with poor prognosis in metastatic state of AGC patients, but further validation of other research is required.

The clinical efficacy and safety of CPT-11+CDDP therapy were studied retrospectively in 34 patients with advanced and recurrent gastric cancer. The overall response rate was 5. 9%; MST was 209 days. The adverse effects observed were grade 3 in 7 patients(20. 6%). CPT-11+CDDP therapy could be useful and safe as third-line chemotherapy.

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.

A 73-year-old man with gastric cancer of Borrmann type 3 accompanied with N3 was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 45 mg/m/2 on day 1 and 15, and S-1 orally at 120 mg/body on day 1 to 7 and day 15 to 21. This treatment was repeated every 28 days as one course. After 4 courses of treatment, a CT scan revealed partial response of the lymph node metastases, and imaging modalities showed complete response of the primary lesion. The serum CEA value normalized after 4 courses of treatment. Toxicities included leukocytopenia (grade 3-4) and neutropenia (grade 3-4). Chemotherapy in the outpatient setting was possible by reduction of dose (DOC 45-->40-->35 mg/m2). Total gastrectomy was performed after 4 courses of treatment. The histological effect of primary lesion was judged to be Grade 2.

Background: We retrospectively evaluated the efficacy of weekly paclitaxel therapy as second-line treatment for patients with advanced gastric cancer that was refractory to S-1., Patients and Methods: In total, 33 patients received intravenous paclitaxel (80 mg m(-2)) on days 1, 8 and 15 as part of a 4-week cycle., Results: Eight patients showed a partial response, 11 showed stable disease and 14 showed disease progression. In total, 171 courses (mean=5.2; range=3-16) were administered. Thirteen cases subsequently underwent third-line treatment. The median survival time and time to progression from the time of second-line treatment was 8.0 months and 4.2 months, respectively. The most common haematological toxicities were leukopenia and neutropenia. Non-haematological toxicities were generally mild to moderate and controllable., Conclusion: This study showed favourable therapeutic outcomes for advanced gastric cancer patients. However, it will be necessary to confirm the advantages of paclitaxel treatment for S-1-refractory advanced gastric cancer in a larger population.