Chemotherapy for advanced gastric cancer.
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ABSTRACT:
SUBMITTER: Wagner AD
PROVIDER: S-EPMC6483552 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Chemotherapy for advanced gastric cancer.
Wagner Anna Dorothea AD Syn Nicholas Lx NL Moehler Markus M Grothe Wilfried W Yong Wei Peng WP Tai Bee-Choo BC Ho Jingshan J Unverzagt Susanne S
The Cochrane database of systematic reviews 20170829
<h4>Background</h4>Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated sig ...[more]
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Project description:To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched. Studies that included patients with metastases at enrollment were excluded. Databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, and American Society of Clinical Oncology meeting abstracts from 1978 to 2010. The censor date was up to April 2010. Primary outcome was the odds ratio (OR) for improving overall survival rate of patients with advanced gastric cancer. Secondary outcome was the OR for down-staging tumor and increasing R0 resection in patients with advanced gastric cancer. Safety analyses were also performed. All calculations and statistical tests were performed using RevMan 5.0 software.A total of 2271 patients with advanced gastric cancer enrolled in 14 trials were divided into NAC group (n = 1054) and control group (n = 1217). The patients were followed up for a median time of 54 mo. NAC significantly improved the survival rate [OR = 1.27, 95% confidence interval (CI): 1.04-1.55], tumor stage (OR = 1.71, 95% CI: 1.26-2.33) and R0 resection rate (OR = 1.51, 95% CI: 1.19-1.91) of patients with advanced gastric cancer. No obvious safety concerns were raised in these trials.NAC can improve tumor stage and survival rate of patients with advanced gastric cancer with a rather good safety.
| S-EPMC2992682 | biostudies-other
Project description:Presently, surgery is the only treatment approach for gastric cancer and improving the prognosis of locally advanced gastric cancer is one of the key factors in promoting gastric cancer survival benefit. The MAGIC study was the first to demonstrate the efficacy of neoadjuvant chemotherapy (NAC) in European countries. In recent years, several clinical trials have provided evidence for the use of NAC in Asian patients with locally advanced gastric cancer. However, clinical practice guidelines vary between Asian and non-Asian populations. Optimal NAC regimens, proper target populations, and predictors of NAC outcomes in Asian patients are still under investigation. Herein, we summarized the current progress in the administration of NAC in Asian patients with gastric cancer.
| S-EPMC9911622 | biostudies-literature
Project description:No standard adjuvant or palliative chemotherapy regimen has been internationally approved for patients with advanced gastric cancer. Adjuvant chemoradiotherapy is administered prior to surgery and is used in the Unitied States, and intensified chemotherapy is administered prior to and after surgery and is used in Europe. Limited D1 dissections are also frequently performed in the United States and Europe. In Korea, patients undergoing D2 resection appear to benefit from postoperative adjuvant chemotherapy using S-1 or capecitabine plus oxaliplatin. Fluoropyrimidine, platinum, taxane, epirubicin, and irinotecan may be employed alone or in combination as a first-line therapy in a palliative chemotherapy regimen. In Asia, an orally administered fluoropyrimidine, such as capecitabine or S-1, is favored over the continuous infusion of 5-fluorouracil because of its convenience. Trastuzumab has been integrated into the current standard chemotherapy for human epidermal growth factor receptor 2-overexpressing gastric cancers. There is currently no standard regimen for secondary palliative chemotherapy. Clinical studies of several targeted therapies are ongoing.
| S-EPMC3724024 | biostudies-other
Project description:Currently, adjunctive therapy for gastric cancer is not standardized worldwide and the most effective combination of different modalities has not been clearly determined. The aim of the present study was to retrospectively analyze the efficacy and toxicity of the combination of perioperative epirubicin, capecitabine and oxaliplatin (EOX) chemotherapy and postoperative concurrent chemoradiotherapy in the treatment of locally advanced gastric cancer. A total of 41 patients with locally advanced gastric cancer who had undergone perioperative EOX chemotherapy and surgical resection followed by chemoradiotherapy, were assessed. The perioperative EOX regimen consisted of 50 mg/m2 epirubicin and 130 mg/m2 oxaliplatin on day 1, with 625 mg/m2 capecitabine administered twice daily on days 1-21. The perioperative regimen was repeated 2-3 times every 3 weeks. After complete resection following the perioperative EOX regimen, concurrent chemoradiotherapy with capecitabine (4,500 cGy in daily fractions of 180 cGy administered 5 days per week for 5 weeks, with 625 mg/m2 capecitabine twice daily during radiotherapy) and 2 cycles of the EOX regimen 4 weeks after radiotherapy, were performed. In total, 30/41 patients (73.2%) completed all the planned treatments, including perioperative chemotherapy, surgical resection and chemoradiotherapy. The effective rate of preoperative chemotherapy (partial and complete response) was 56.1%; 30/41 patients received R0 resection, and the overall 3-year survival rate was 57.7%. Grade 3/4 gastrointestinal toxicity (nausea/vomiting) occurred in 22% of the patients, while 18 patients (43.9%) developed grade 3/4 hematological toxicity (granulocytopenia). The results of the present study indicated that the combination of perioperative EOX chemotherapy and postoperative concurrent chemoradiotherapy is feasible and effective for locally advanced gastric cancer.
| S-EPMC5532677 | biostudies-other
Project description:BackgroundNivolumab therapy is a standard-of-care treatment for heavily pretreated patients with advanced gastric cancer (AGC). Previous studies have reported improvement in the objective response rate to chemotherapy after nivolumab therapy for other types of cancer. This study evaluated the efficacy and safety of chemotherapy after nivolumab therapy in AGC.Patients and methodsWe conducted a prospective, multicenter, observational study in pretreated patients with nivolumab-refractory or -intolerant AGC. Patients received irinotecan, oxaliplatin-containing regimens, or trifluridine/tipiracil. The primary endpoint was overall survival.ResultsA total of 199 patients were included (median age: 69 years; male: 70%; female: 30%). Median overall survival and progression-free survival were 7.5 months [95% confidence interval (CI): 6.7-9.7 months] and 2.9 months (95% CI: 2.2-3.5 months), respectively. Objective response and disease control rates were 16.8% (95% CI: 11.6% to 23.6%) and 18.9% (95% CI: 38.9% to 54.6%), respectively. A prognostic index using alkaline phosphatase and the Glasgow Prognostic Score was generated to classify patients into three risk groups (good, moderate, and poor). The hazard ratios of the moderate and poor groups to the good group were 1.88 (95% CI: 1.22-2.92) and 3.29 (95% CI: 1.92-5.63), respectively. At the initiation of chemotherapy, 42 patients had experienced immune-related adverse events due to prior nivolumab therapy. The most common grade 3-4 adverse events were neutropenia (7.5%), anemia (8.0%), and anorexia (7.5%).ConclusionsThe administration of cytotoxic chemotherapy after nivolumab therapy may give rise to a synergistic antitumor effect in AGC. Further investigation is warranted to confirm these findings.
| S-EPMC10774960 | biostudies-literature
Project description:Background The relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients. Methods Data were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications. Results This cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22–28 days and 29–35 days groups revealed a better OS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.185; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.004; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.022) and PFS (≤21 vs. 22–28 days: HR 1.54, 95% CI = 0.81–2.93, P = 0.256; 36–42 vs. 22–28 days: HR 2.20, 95% CI = 1.28−3.79, P = 0.111; 43–84 vs. 22–28 days: HR 1.83, 95% CI = 1.09–3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22–35 days (OS: HR 1.78 95% CI = 1.25−2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07−2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS. Conclusion Patients who received surgery within 3−5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted.
| S-EPMC7773852 | biostudies-literature
Project description:PurposeThe KEYNOTE-062 trial demonstrated the efficacy and safety of pembrolizumab for advanced gastric cancer (GC). The current study evaluated the cost-effectiveness of pembrolizumab alone or in combination with chemotherapy versus chemotherapy for advanced GC from the perspective of the United States and China. And the results will provide evidence and data support for more drug selection-related decisions and research in the future.MethodsA partitioned survival approach with three states was created for treatment of advanced GC. The survival data were derived from KEYNOTE-062 trial and the individual patient data were generated by a specific algorithm. We fitted 21 survival functions to each treatment arm and selected the most suitable distribution type for each one. Direct costs and utility values were collected from the published, available database. Cost, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs) were considered as the primary measure outcomes. One-way and probabilistic sensitivity analyses were performed to assess the reliability of the analyses.ResultsIn the base-case analysis of combined positive score (CPS) ≥1 patients, the ICUR of pembrolizumab plus chemotherapy versus chemotherapy in American and Chinese setting is $345,209/QALY and $186,802.6/QALY, respectively. And the ICUR of pembrolizumab versus chemotherapy is $473,650/QALY and $377,753/QALY in the context of the US and China, respectively. For CPS≥10 patients, the ICUR of pembrolizumab plus chemotherapy versus chemotherapy in American and Chinese setting is $483,742/QALY and $262,965/QALY, respectively. And that of pembrolizumab versus chemotherapy is $96,550/QALY and $67,896/QALY in the context of the US and China.ConclusionCompared with chemotherapy, either pembrolizumab plus chemotherapy or pembrolizumab monotherapy is not regarded as a cost-effective strategy for patients with CPS≥1, advanced gastric cancer in the current American and Chinese setting. But pembrolizumab monotherapy for CPS≥10 patients would become a cost-effective option in the American setting.
| S-EPMC10557869 | biostudies-literature
Project description:BackgroundSerum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.MethodsIn total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.ResultsPre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).ConclusionsCA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
| S-EPMC7786973 | biostudies-literature
Project description:BackgoundLittle information regarding to the survival advantage of third-line chemotherapy in advanced gastric cancer patients is available. The current study is designed to systematically review and perform meta-analysis on the effect of third-line chemotherapy on progressive or recurrent gastric cancer treatment.MethodsAfter thorough searching of online databases, total 20 articles were included into qualitative systematic review and 6 of them were used to conduct qualitative meta-analysis.ResultsIt was found that the third-line chemotherapy was superior to placebo or best supportive care in terms of prolonging median oval survival (OS) length and progress free survival (PFS) length (Hedges's g for OS = -0.315 ± 0.077, P < .001; and for PFS = -0.382 ± 0.098, P < .001). In addition, the third-line chemotherapy was favored (Hedges's g = 0.848, P < .001) in terms of overall survival rate (Hazard ratio = 0.679, 95% confidence interval: 0.565-0.816, P < .001) or tumor free survival rate (Hazard ratio = 0.561, 95% confidence interval: 0.444-0.709, P < .001).ConclusionThe third-line chemotherapy is superior to the best supportive care in advanced gastric cancer patients who had been pretreated with first-line and second-line chemotherapy.
| S-EPMC5478304 | biostudies-literature
Project description:The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.
| S-EPMC6954129 | biostudies-literature