Clinical Trials of Antiangiogenesis Therapy on Gastric Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu LC
PROVIDER: S-EPMC5154210 | biostudies-literature | 2008 Dec
REPOSITORIES: biostudies-literature
Publications
Clinical Trials of Antiangiogenesis Therapy on Gastric Cancer.
Wu Li Cun LC Zhang Wei Dong WD
Gastroenterology research 20081120 1
Both malignant tumor growth and metastasis are dependent upon angiogenesis, a process of new blood vessel formation. Inhibition of this process by specific inhibitors might be able to control tumor growth and metastasis. Therefore, antiangiogenesis thereapy is considered a promising strategy and being studied worldwide. A wide variety of angiogenesis inhibitors have been identified and some of them are under clinical trials in the advanced patients with cancer including gastric cancer. This revi ...[more]
Similar Datasets
Project description:Novel antiangiogenic agents currently being developed may ultimately be more effective against solid tumours and less toxic than cytotoxic chemotherapy. As a result of the early clinical trials of angiogenesis inhibitors, investigators are beginning to appreciate the complexity of targeting angiogenesis and the realisation that developing clinically useful antiangiogenic therapy will be more challenging than originally thought. It is now apparent that new methods and surrogate markers to assess these agents' biological activity are crucial for their successful development. This review summarises the currently available clinical data on the development of surrogate markers of angiogenesis inhibitors.
| S-EPMC2394225 | biostudies-other
Project description:Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.
| S-EPMC9810618 | biostudies-literature
Project description:Antiangiogenesis therapy has been demonstrated to prolong the free survival with tolerable toxicity. However the efficacy of these drugs in overall survival (OS) remains controversial. This study was designed to assess the overall performance of antiangiogenesis therapy in improving the survival of ovary cancer (OC) patients.Electronic database of PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to identify relevant clinical randomized control trial (RCTs) assessing the therapeutic value of antiangiogenesis therapy in OC patients during 2011 to 2017. Additionally, abstracts of annual meetings were also conducted. Only English articles were considered. Progression free survival (PFS), OS, and objective response rate (ORR) were obtained from eligible RCTs. The HRs for time-to-event variables and ORs for dichotomous outcomes with their 95% CIs were used for this meta-analysis. All the statistical analyses were carried out by Stata 11.0 software using a fixed or random-models according to heterogeneity.A total of 15 RCTs including 9359 patients were recruited into this meta-analysis. Addition of antiangiogenic agents improved PFS (HR?=?0.71, 95% CI 0.62-0.81, P?<?.001), OS (HR?=?0.92, 95% CI 0.86-0.98, P?=?.008) and ORR (OR?=?1.74, 95% CI 1.27-2.39, P?=?.001) compared to placebo or chemotherapy alone in overall analysis. Antiangiogenic agents prolonged both PFS (HR?=?0.58, 95% CI 0.52-0.65, P?=?.000) and OS (HR=0.84, 95% CI 0.76-0.92, P?=?.000) in recurrent settings but only PFS in primary settings (HR?=?0.88, 95% CI 0.79-0.98, P?=?.020), longer PFS and OS in both platinum-sensitive recurrent patients (HR?=?0.56, 95% CI 0.48-0.64, P?=?.000, PFS; HR?=?0.86, 95% CI 0.76-0.98, P?=?.027, OS) as well as platinum-resistant recurrent cases (HR?=?0.54, 95% CI 0.41-0.71, P?=?.000, PFS; HR?=?0.84, 95% CI 0.71-0.98, P?=?.029, OS). Throughout therapy improved PFS (HR?=?0.66, 95% CI 0.57-0.76, P?<?.001) and OS (HR?=?0.89, 95% CI 0.83-0.96, P?=?.001). However the maintenance therapy of antiangiogenic agents was irrelevant to a longer PFS or OS.Based on the available studies, antiangiogenic agents play an important role in the survival of OC patients. More randomized controlled trials are needed to reach more convinced conclusion.
| S-EPMC6112884 | biostudies-literature
Project description:The process of new blood vessel formation, or angiogenesis, has become an important target for therapeutic intervention in many cancers, including metastatic colorectal cancer (mCRC). The growth and metastasis of primary tumors is dependent upon their ability to acquire and maintain an adequate blood supply; however, angiogenesis in tumors is an irregular process leading to chaotic and hyperpermeable vessels that may result in increased intratumoral pressure and poor exchange of macromolecules and oxygen. It has been hypothesized that inhibition of angiogenesis in tumors can both impair the formation of new tumor blood vessels and possibly 'normalize' the existing tumor vasculature, causing a more efficient delivery of cytotoxic chemotherapies (CTs). Over the last decade, therapies that target vascular endothelial growth factor (VEGF) have become a component of treatment for several cancers. In particular, the combination of bevacizumab with established chemotherapeutic regimens for mCRC has been shown to improve overall and progression-free survival, as well as response rates, over CT alone. Agents that target various members of the VEGF family, as well as signaling by the VEGF receptors and their tyrosine kinase components, are currently under development and evaluation in clinical trials. Integration of these new therapies into the treatment of mCRC will ultimately increase the available therapeutic options for patients. Still, many challenges remain, including identifying and validating relevant biomarkers to guide the optimal use of antiangiogenesis agents.
| S-EPMC3481559 | biostudies-literature
Project description:Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials.The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score.Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited ≥50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals.This study provides greater understanding of clinicians' attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual.
| S-EPMC3101903 | biostudies-other
Project description:BackgroundGastric cancer (GC) is the third most common cause of malignancy associated mortality globally. The cornerstone of curative treatment involves surgical gastrectomy. In this study, we explore clinical trials involving gastrectomy for GC, highlighting inadequacies and underlining promising surgical interventions and strategies.Materials and methodsOn 1 May 2020, ClinicalTrials.gov was explored for interventional trials related to gastrectomy for GC, without adding limitations for location or date. All data pertaining to the trials were collected. Characteristics such as phase, duration, enrolment size, location, treatment allocation, masking and primary endpoint were analysed.ResultsOne hundred thirty-eight clinical trials met the search criteria. Clinical trials were performed in only 14 countries; most of them occurring in China. Most trials (33%) were still in the recruiting phase. On average, the length of trials was 3.9 years. Most trials had parallel assignment, were randomised and masked. The primary endpoint which was mostly commonly studied was overall survival (33%). The most common intervention studied is laparoscopic gastrectomy in 43 (31%) trials.ConclusionsOur study exposed a small number of trials, publication rate, absence of geographic variety in clinical trials involving gastrectomy for GC. Adequate management of trial design can help decrease duration and increase validity of results. More trials comparing different surgical techniques are needed to update the surgical practice of gastrectomy for GC.
| S-EPMC8183643 | biostudies-literature
Project description:Gastric cancer is the third leading cause of cancer mortality worldwide. As surgery is the only curative treatment strategy and conventional chemotherapy has shown limited efficacy -with a median overall survival of 10 months- new treatments are urgently needed. Trastuzumab and Ramucirumab (targeting HER2 and VEGFR2, respectively) are the only targeted therapies approved so far. Indeed, most Phase III clinical trials evaluating molecular drugs in gastric cancer failed. This review will retrace the relevant clinical trials with molecular therapies performed in gastric cancer patients, discussing the possible reasons for their failure and indicating new perspective for a real improvement of the treatment of this disease.
| S-EPMC5593674 | biostudies-literature
Project description:ImportanceThe results of numerous large randomized clinical trials (RCTs) have changed clinical practice in gastric cancer (GC). However, research waste (ie, unpublished data, inadequate reporting, or avoidable design limitations) is still a major challenge for evidence-based medicine.ObjectivesTo determine the characteristics of GC RCTs in the past 20 years and the presence of research waste and to explore potential targets for improvement.Design, setting, and participantsIn this cross-sectional study of GC RCTs, ClinicalTrials.gov was searched for phase 3 or 4 RCTs registered from January 2000 to December 2019 using the keyword gastric cancer. Independent investigators undertook assessments and resolved discrepancies via consensus. Data were analyzed from August through December 2020.Main outcomes and measuresThe primary outcomes were descriptions of the characteristics of GC RCTs and the proportion of studies with signs of research waste. Research waste was defined as unpublished data, inadequate reporting, or avoidable design limitations. Publication status was determined by searching PubMed and Scopus databases. The adequacy of reporting was evaluated using the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline checklist. Avoidable design limitations were determined based on existing bias or lack of cited systematic literature reviews. In the analyses of research waste, 125 RCTs that ended after June 2016 without publication were excluded.ResultsA total of 262 GC RCTs were included. The number of RCTs increased from 25 trials in 2000 to 2004 to 97 trials in 2015 to 2019, with a greater increase among RCTs of targeted therapy or immunotherapy, which increased from 0 trials in 2000 to 2004 to 36 trials in 2015 to 2019. The proportion of RCTs that were multicenter was higher in non-Asian regions than in Asian regions (50 of 71 RCTs [70.4%] vs 96 of 191 RCTs [50.3%]; P = .004). The analysis of research waste included 137 RCTs, of which 81 (59.1%) were published. Among published RCTs, 65 (80.2%) were judged to be adequately reported and 63 (77.8%) had avoidable design defects. Additionally, 119 RCTs (86.9%) had 1 or more features of research waste. Study settings that included blinding (odds ratio [OR], 0.56; 95% CI, 0.33-0.93; P = .03), a greater number of participants (ie, ≥200 participants; OR, 0.07; 95% CI, 0.01-0.51; P = .01), and external funding support (OR, 0.22; 95% CI, 0.08-0.60; P = .004) were associated with lower odds of research waste. Additionally, 35 RCTs (49.3%) were referenced in guidelines, and 18 RCTs (22.2%) had their prospective data reused.Conclusions and relevanceTo our knowledge, this study is the first to describe the characteristics of GC RCTs in the past 20 years, and it found a research waste burden, which may provide evidence for the development of rational RCTs and reduction of waste in the future.
| S-EPMC8449283 | biostudies-literature
Project description:Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.
| S-EPMC4736909 | biostudies-literature
Project description:The human body and its microbiome constitute a highly delicate system. The gut microbiome participates in the absorption of the host's nutrients and metabolism, maintains the microcirculation, and modulates the immune response. Increasing evidence shows that gut microbiome dysbiosis in the body not only affects the occurrence and development of tumors but also tumor prognosis and treatment. Microbiome have been implicated in tumor control in patients undergoing anti- angiogenesis therapy and immunotherapy. In cases with unsatisfactory responses to chemotherapy, radiotherapy, and targeted therapy, appropriate adjustment of microbes abundance is considered to enhance the treatment response. Here, we review the current research progress in cancer immunotherapy and anti- angiogenesis therapy, as well as the unlimited potential of their combination, especially focusing on how the interaction between intestinal microbiota and the immune system affects cancer pathogenesis and treatment. In addition, we discuss the effects of microbiota on anti-cancer immune response and anti- angiogenesis therapy, and the potential value of these interactions in promoting further research in this field.
| S-EPMC8566949 | biostudies-literature