Treatment Of Advanced Gastric Carcinoma Research Articles

Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression.

Anti-PD-1 immunotherapy has emerged as an important therapeutic modality in advanced gastric cancer (GC). However, drug resistance frequently develops, limiting its effectiveness. The role of gastric cancer mesenchymal stem cells (GCMSCs) in anti-PD-1 resistance was evaluated in vivo in NPGCD34+ or NCGPBMC xenograft mouse model. In addition, we investigated CD8+T cell infiltration and effector function by spectral cytometry and IHC. The effects of GCMSCs conditional medium (GCMSC-CM) on GC cell lines were characterized at the level of the proteome, secretome using western blot, and ELISA assays. We reported that GCMSCs mediated tolerance mechanisms contribute to tumor immunotherapy tolerance. GCMSC-CM attenuated the antitumor activity of PD-1 antibody and inhibited immune response in humanized mouse model. In GC cells under serum deprivation and hypoxia, GCMSC-CM promoted GC cells proliferation via upregulating PD-L1 expression. Mechanistically, GCMSC-derived IL-8 and AKT-mediated phosphorylation facilitated HK2 nuclear localization. Phosphorylated-HK2 promoted PD-L1 transcription by binding to HIF-1α. What is more, GCMSC-CM also induced lactate overproduction in GC cells in vitro and xenograft tumors in vivo, leading to impaired function of CD8+ T cells. Furthermore, CXCR1/2 receptor depletion, CXCR2 receptor antagonist AZD5069 and IL-8 neutralizing antibody application also significantly reversed GCMSCs mediated immunosuppression, restoring the antitumor capacity of PD-1 antibody. Our findings reveal that blocking GCMSCs-derived IL-8/CXCR2 pathway decreasing PD-L1 expression and lactate production, improving antitumor efficacy of anti-PD-1 immunotherapy, may be of value for the treatment of advanced gastric carcinoma.

Tislelizumab combined with anlotinib and chemotherapy (XELOX) in the treatment of advanced gastric carcinoma: Preliminary results of a single-arm, open-label phase I/IIa trial (TALENT study).

396 Background: PD-1 inhibitor combined with chemotherapy is one of the standard regimens for first line gastric. The addition of anti-vascularization agents has been reported to help improve the overall survival (OS) in GC/GEJC patients (pts) through vascular-normalization in the microenvironment. In this phase I/IIa study, we aim to explore the safety and efficacy of tislelizumab combined with anlotinib and XELOX (TAXE regimen) as first line treatment for advanced GC/GEJC. Methods: This prospective, multicenter, phase I/IIa study planned to enroll 9 patients in phase I and 57 patients in Phase IIa. The aim of this Phase 1 study was to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and safety of 8 mg, 10 mg or 12 mg anlotinib in combination with XELOX and tislelizumab. The maximum tolerable dosage (MTD) would be administered to all pts in phase II. The primary and objective response rate(ORR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), OS, and safety. The exploring endpoint was to evaluate the association between the efficacy and the expression of biomarkers including PD-L1, microsatellite instability profile, and genome stability (GS). Results: From march 2021 to August 2022, 38 pts were enrolled (9 pts in phase 1). Phase 1 was completed without dosage limiting toxicities (DLTs). 12mg anlotinib was recommended for phase 2. Thirty two (84.21%) pts had at least one treatment-related adverse events (TRAEs), and 7 patients (18.42%) had at least one grade 3/4 TRAEs. Anemia (15 pts, 39.47%), leukopenia (12 pts, 31.58%) and fatigue (10 pts, 26.32%) were the most common TRAEs. Two pts achieved complete response (CR), 20 pts achieved partial response (PR), and 7 pts achieved stable disease (SD). The ORR was 75.86% (95% CI: 57.89%-87.78%), and the DCR was 100%. Conclusions: The preliminary results of this Phase I/IIa trial by using tislelizumab combined with anlotinib and XELOX had shown great potential in improving the response rate in advanced GC/GEJC patients with manageable toxicity. Clinical trial information: NCT04963088 .

Safety Analysis of Apatinib Combined with Chemotherapy in the Treatment of Advanced Gastric Carcinoma: A Randomised Controlled Trial.

Objective To study the safety of apatinib combined with chemotherapy in the treatment of advanced gastric carcinoma (GCA). Methods 74 patients with advanced GCA treated in the oncology department of Weifang People's Hospital (January 2019–January 2020) were enrolled in this study and equally split into study group (SG) and reference group (RG) according to the odd and even admission numbers. RG underwent chemotherapy alone, while SG received apatinib combined with chemotherapy. The clinical indicators of serum matrix metalloproteinase 9 (MMP-9), serum interleukin-2 receptor (SIL-2R), and immune cell level were detected in the two groups before and after treatment to analyze the therapeutic effect of different treatment methods on patients with advanced gastric carcinoma. Results No obvious differences in gender ratio, average age, average BMI, pathological staging, pathological types, organ metastasis types, and residence were observed between the two groups (P > 0.05). The short-term follow-up results showed that the disease control rate (DCR) in SG was markedly higher compared with RG (P < 0.05). The MMP-9 and SIL-2R levels in both groups after treatment decreased (P < 0.05), and the levels in SG after treatment were notably lower compared with RG (P < 0.001). Compared with RG, CD3+, CD4+, and CD4+/CD8+ levels in SG after treatment were notably higher (P < 0.001), while the CD8+ level was notably lower (P < 0.001). The median progression-free survival (MPFS) and overall survival (OS) in SG were markedly higher compared with RG (P < 0.001). The GQOLI-74 scores in both groups after treatment increased (P < 0.001), and the GQOLI-74 score in SG after treatment was markedly higher compared with RG (P < 0.001). The total incidence of adverse reactions was lower in SG than in RG (P < 0.05). Conclusion Apatinib combined with chemotherapy is superior to chemotherapy alone in effectively improving treatment outcomes in patients with advanced GCA.

Nursing Mode for Advanced Gastric Carcinoma with Combined Application of Domestic Tegafur Gimeracil Oteracil Potassium and Oxaliplatin

To observe and analyze the nursing method for advanced gastric carcinoma with combined application of domestic tegafur gimeracil oteracil potassium and oxaliplatin. 160 patients who had been diagnosed with advanced gastric carcinoma in our hospital were selected as research objects and all of them were applied with therapy of domestic tegafur gimeracil oteracil potassium and oxaliplatin. During treatment, targeted nursing mode was implemented to overcome relevant toxic reaction. The nursing effect was observed and analyzed. After implementation of nursing, all patients were applied with chemotherapy regimen successfully and the total treatment effective rate reached 78.13 %. During treatment with combined application of domestic tegafur gimeracil oteracil potassium and oxaliplatin, the main toxic reactions were peripheral neurotoxicity, leukopenia, thrombocytopenia, diarrhea, nausea, vomiting, phlebitis, etc. The comparison of mental status score before and after nursing showed that the mental status was significantly better after nursing, p<0.05. During treatment of advanced gastric carcinoma with combined application of domestic tegafur gimeracil oteracil potassium and oxaliplatin, implementing targeted nursing can significantly reduce toxic reactions.

Postoperative Curative Effect of Docetaxel and Nedaplatin Combined Chemotherapy in Advanced Gastric Carcinoma

The present study was aimed to analyze the postoperative curative effect of combined chemotherapy with docetaxel and nedaplatin in advanced gastric carcinoma. In this study, 160 patients with advanced gastric carcinoma were enrolled as study subjects. They underwent radical gastrectomy and were randomly divided into the study group and the control group, each containing 80 patients. The control group was treated with oxaliplatin, leucovorin and 5-fluorouracil combined chemotherapy. The study group was treated with docetaxel, nedaplatin combined chemotherapy. There was no significant difference in short-term treatment efficiency between the two groups. In terms of 1-year survival rate and 3-year survival rate, the study group was better than the control group, p<0.05. There was no significant different in rate of adverse reactions between the two groups. The study group showed better quality of life relative to the control group. For treatment of advanced gastric carcinoma, docetaxel-nedaplatin combination could achieve relatively satisfactory long-term efficacy

Observation of Postoperative Curative Effect of Docetaxel Nedaplatin Combined Chemotherapy in Advanced Gastric Carcinoma

This study aims to analyze the postoperative curative effect of the combination chemotherapy with docetaxel and nedaplatin for advanced gastric carcinoma. In this study, 160 patients with advanced gastric carcinoma were enrolled. They underwent radical gastrectomy and randomly divided into the study group and the control group, each containing 80 patients. The control group was treated with oxaliplatin, leucovorin and 5-fluorouracil combined chemotherapy. The study group was treated with docetaxel, nedaplatin combined chemotherapy. There was no significant difference in short-term treatment efficiency between these 2 groups. In terms of 1-y and 3-y survival rates, the study group was significantly better than the control group. There was no significant different in rate of adverse reactions between these 2 groups. The study group showed higher quality of life than the control group. For treatment of advanced gastric carcinoma, docetaxel nedaplatin combined chemotherapy could yield good results and relatively better long-term efficacy.

Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer

Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma and some other solid tumors. However, the direct functional mechanisms of tumor lethality mediated by apatinib have not yet been fully characterized, and the precise mechanisms of drug resistance are largely unknown. Here, in this study, we demonstrated that apatinib could induce both apoptosis and autophagy in human colorectal cancer (CRC) via a mechanism that involved endoplasmic reticulum (ER) stress. Moreover, activation of the IRE1α pathway from apatinib-induced ER stress is responsible for the induction of autophagy; however, blocking autophagy could enhance the apoptosis in apatinib-treated human CRC cell lines. Furthermore, the combination of apatinib with autophagy inhibitor chloroquine (CQ) tends to have the most significant anti-tumor effect of CRC both in vitro and in vivo. Overall, our data show that because apatinib treatment could induce ER stress-related apoptosis and protective autophagy in human CRC cell lines, targeting autophagy is a promising therapeutic strategy to relieve apatinib drug resistance in CRC.

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets.

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

Neoadjuvant or adjuvant therapy for gastric cancer.

Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. In the United States, where a limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In Europe, intensified perioperative chemotherapy is commonly administered. In Japan and South Korea, postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. Several ongoing trials are currently evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as well as the place of targeted therapeutic agents in the treatment of advanced gastric carcinoma.

Impact of neoadjuvant chemotherapy with PELF-protocoll versus surgery alone in the treatment of advanced gastric carcinoma

BackgroundIn a retrospective study we analyzed the impact of neoadjuvant chemotherapy (CTx) with the PELF - protocol (Cisplatin, Epirubicin, Leukovorin, 5-Fluoruracil) on mortality, recurrence and prognosis of patients with advanced gastric carcinoma, UICC stages Ib-III.Methods64 patients were included. 26 patients received neoadjuvant CTx followed by surgical resection, 38 received surgical resection only. Tumor staging was performed by endoscopy, endosonography, computed tomography and laparoscopy. Patients staged Ib – III received two cycles of CTx according to the PELF-protocol. Adjuvant chemotherapy was not performed at all.ResultsComplete (CR) or partial response (PR) was seen in 20 patients (77%), 19% showing CR and 58% PR. No benefit was observed in 6 patients (23%). Two of these 6 patients displayed tumor progression during CTx. Major toxicity was defined as grade 3 to 4 neutropenia or gastrointestinal side effects. One patient died under CTx because of neutropenia and was excluded from the overall patient collective. The curative resection rate was 77% after CTx and 74% after surgery only. The perioperative morbidity rate after CTx was 39% versus 66% after resection only. Recurrence rate after CTx was 38% and 61% after surgery alone; we detected an effective reduction of locoregional recurrence (12% vs. 26%). The overall survival was 38% after CTx and 42% after resection only. The 5-year survival rates were 45% in responders, 20% in non - responders and 42% in only resected patients. A subgroup analysis indicates that responders with stage III tumors may benefit with respect to their 5-year survival in comparable patients without neoadjuvant CTx. As to be expected, non-responders with stage III tumors did not benefit with respect to their survival. The 5-year-survival was approximated using a Kaplan-Meier curve and compared using a log-rank test.ConclusionIn patients with advanced gastric carcinoma, neoadjuvant CTx with the PELF- protocol significantly reduces the recurrence rate, especially locoregionally, compared to surgery alone. In our study, there was no overall survival benefit after a 5-year follow-up period. Alone a subgroup of patients with stage III tumors appear to benefit significantly in the long term from neoadjuvant CTx.

S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for advanced gastric carcinoma: a meta-analysis.

BackgroundAlthough both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. MethodsPubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. ResultsFive randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There’re no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed.ConclusionS-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.

Immunotherapy with Cytokine-Induced Killer Cells as an Adjuvant Treatment for Advanced Gastric Carcinoma: A Retrospective Study of 165 Patients

Cytokine-induced killer (CIK) cells have demonstrated antitumor effects in vitro and in vivo. The purpose of this study was to evaluate the effect of CIK cell treatment as an adjuvant immunotherapy on the prognosis of gastric carcinoma in patients after surgery. The patients with stage II-III gastric carcinoma after gastrectomy, including 53 patients receiving autologous CIK cell treatment combined with chemotherapy (CIK group) and 112 patients in the corresponding period receiving chemotherapy alone (control group), were retrospectively studied. The patients in the CIK group were matched to those in the control group regarding the sex and age of patients, tumor site, histological type, pathological grade, tumor size, clinical stage, and chemotherapy plan. Progression-free survival (PFS) and overall survival (OS) were evaluated. The 5-year OS rate in the CIK group was significantly improved compared to that in the control group (56.6% vs. 26.8%, p=0.014). The 5-year PFS rate in the CIK group was also significantly improved compared to that in the control group (49.1% vs. 24.1%, p=0.026). The median PFS (36.0 months) and OS (96.0 months) in the CIK group were significantly prolonged than those in the control group (23.0 months for median PFS and 32.0 months for median OS, p=0.028 and p=0.003). No serious side effect was observed in the CIK group. This study suggests that immunotherapy with CIK cells may serve as an adjuvant treatment to prolong the survival of patients with stage II-III gastric carcinoma.

The clinical research of elemene emulsion combined with FOLFOX4 regimen in the treatment of advanced gastric carcinoma

Objective The aim of this study was to observe the effects and adverse reactions of elemene emulsion added to the chemotherapy in the treatment of advanced gastric carcinoma (AGC).

Weekly regimen of paclitaxel liposome combined with cisplatin and 5-fluorouracil continuous infusion in the treatment of advanced gastric carcinoma

To evaluate the efficacy and toxicity of paclitaxel with low-dose cisplatin and 5-fluorouracil continuous infusion in the treatment of advanced gastric carcinoma. The patients were treated with paclitaxel liposome 60 mg/m(2) i.v. gtt on d1, 8, 15, DDP 15 mg×m(-2)×d(-1) by i.v. gtt on d1-5, 5-Fu 500 mg×m(-2)×d(-1) by civ for 120 h, administered every 21 days. Out of the whole group, 3 cases achieved CR, 29 cases achieved PR with an ORR of 54.2% and median TTP of 7.1 months. Out of 40 cases in the primary treatment, 3 cases achieved CR, 22 cases achieved PR with an ORR of 62.5% and median TTP of 7.6 months. Out of 20 evaluable retreated cases, no case achieved CR, 7 cases achieved PR with an ORR of 36.8% and median TTP 6.3 months. The main toxicities were hematological toxicities, nausea and vomiting of grade I-II. The combination regimen of paclitaxel, low-dose cisplatin and 5-fluorouracil is effective and well tolerated for patients with advanced gastric carcinoma, especially for primary treatment cases. It is worthy of further study.

17. Heterogeneity of HER2 overexpression in gastric dysplasia and carcinoma in an Australian cohort

Background Trastuzumab has been approved in Europe for the treatment of advanced gastric carcinoma. There is a need to accurately identify HER2 status in gastric cancer. The issues of morphologic and molecular heterogeneity and HER2 expression in dysplasia have not been addressed. Aims To assess HER2 status and heterogeneity in gastric dysplasia and carcinoma in paired biopsies and gastrectomies. Methods Gastric carcinoma with biopsies and gastrectomies between January 2000 and December 2009 were retrieved from the PathWest archives. Immunohistochemistry (IHC) for HER2 was performed on gastrectomy tumour blocks, and assessed for HER-2 overexpression and heterogeneity. SISH was performed in 11 cases showing at least 1+ reaction. HER-2 and SISH was performed in biopsies from 3 cases which showed HER2 over-expression on gastrectomy. Results There were 89 cases of gastric carcinoma with paired biopsy and gastrectomy specimens. Sixteen of 89 (18.0%) showed HER2 overexpression (2+ or 3+) on IHC, including 5 cases where reactivity was limited to dysplastic epithelium. Of 44 cases with dysplasia, HER2 overexpression was observed in dysplastic epithelium in 10 (22.7%), and not seen in benign mucosa in any case. Heterogeneity of HER2 overexpression in invasive carcinoma was noted in all cases. The proportion of IHC 2+/3+ clones varied from less than 25% (n = 3), 25–50% (n = 3), 50–75% (n = 2) to >75% (n = 3). SISH confirmed HER2 amplification in 7 of 8 IHC positive cases (6/6 3+, 1/2 2+), and no amplification in 3 tumours with 1+ staining. SISH amplification correlated with the areas of IHC overexpression in all. All biopsies from three HER2 positive tumours demonstrated HER2 overexpression/amplification, including two cases where HER2 + clones accounted for Conclusions 1. HER2 status is comparable to previous studies in gastric carcinoma with good concordance between HER2 3+ overexpression and HER2 amplification. 2. Heterogeneity of tumour HER2 overexpression/amplification may have important implications for HER2 testing in biopsies with the potential for false negative results. 3. HER2 positive dysplasia with negative invasive carcinoma raises issues regarding its role in pathogenesis, and the potential for false positive biopsies. 4. HER2 overexpression appears sufficiently specific to be considered a potential biomarker of dysplasia although the sensitivity is low.

Targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell

Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Studies in recent years indicated that survivin(sur) expression was associated with the biological behaviors of gastric carcinoma. In the present study, targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell were investigated, the recombinant pSCT vector containing CD and TK genes driven by sur promoter was constructed and transfected into SGC-7901 cells. After adding the CCV and 5-FC, the effects of double suicide genes on cell growth, cell cycle and proliferation were determined by MTT assay and flow cytometry (FCM). The results showed that sur promoter could specifically drive the expression of double CD/TK gene in SGC-7901 cells, whereas not in the normal GES-1 cell. After using CCV and 5-FC, the growth of SGC-7901 cells was inhibited. G1 phase proportion was significantly higher in SGC-7901 cells transfected with double suicide genes than the untransfected cells. These results suggest that CD and TK double suicide genes driven by sur promoter could provide a new approach for enhancing selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.

Docetaxel combined with oral etoposide as second-line treatment for advanced gastric carcinoma after failure of platinum- and fluoropyrimidine-based regimens

Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC. Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m(2) as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m(2) once daily on days 1-5, every 3 weeks until disease progression or unacceptable toxicities. Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32-77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5-3.5). Median overall survival was 6 months (95% CI, 3.8-8.2) with 16.9% 1-year survival rate. Grade 3-4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%). Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

Role of docetaxel in the treatment of advanced gastric carcinoma

With a median survival of 9-11 months, advanced gastric cancer represents one of the most aggressive neoplastic disease in western Countries. Radical surgery is considered the cornerstone for any curative procedure, however only a relatively small proportion of resected cases can be considered cured after surgery. In the last few years research data suggested that advanced gastric cancer can be classified into 2 distinct clinical categories: locally advanced (nonmetastatic, non resectable) and metastatic. While the therapeutic goal in the metastatic setting is palliation and survival improvement, in locally advanced cases one of the main goals of the treatment should be response with the aim to make resectable what was unresectable. The introduction of docetaxel for the treatment of advanced gastric cancer represented then a crucial step forward for the cure of this disease with an improvement in both survival and response rate. In this article we reviewed past and ongoing trials using docetaxel in gastric cancer with the aim to delineate a possible effective strategy for the treatment of this tumour

Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens

To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m(2) twice daily (1,650 mg/m(2) per day) on days 1-14 and paclitaxel 175 mg/m(2) by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41-84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2-55.7%) with one complete response and 42.3% (95%CI = 17.2-55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4-4.5 months). Median overall survival was 7.5 months (95%CI = 6-10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11-18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts.

Side effects during treatment of advanced gastric carcinoma by chemotherapy combined with CIK-cell transfusion in elderly people

Objective To study the side effects and therapeutic results of autologous cytokine-induced killer (CIK) cell treatment in elderly patients with advanced gastric cancer.