Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

2018 ◽  
pp. 280-291 ◽  
Author(s):  
Elizabeth Cartwright ◽  
Florence K. Keane ◽  
Peter C. Enzinger ◽  
Theodore Hong ◽  
Ian Chau
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Global Consensus ◽  
Esophagogastric Cancer ◽  
Genetic Features ◽  
Related Mortality ◽  
Optimal Treatment Strategy

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

scholarly journals Combined Therapy of Locally Advanced Oesophageal and Gastro–Oesophageal Junction Adenocarcinomas: State of the Art and Aspects of Predictive Factors

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4591
Author(s):  
Milan Vošmik ◽  
Jindřich Kopecký ◽  
Stanislav John ◽  
Ondřej Kubeček ◽  
Petr Lochman ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Combined Therapy ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Preoperative Chemoradiotherapy ◽  
Current Treatment ◽  
Her2 Status ◽  
Perioperative Chemotherapy ◽  
Optimal Treatment Strategy

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

scholarly journals The interaction between equipoise and logistics in clinical trials: A case study

2017 ◽  
Vol 14 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Meredith G Warshaw ◽  
Vincent J Carey ◽  
Elizabeth J McFarland ◽  
Liza Dawson ◽  
Elaine Abrams ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Standard Of Care ◽  
Design Stage ◽  
Ethical Review ◽  
Clinical Equipoise ◽  
Expert Clinician ◽  
Barriers To Enrollment

Introduction: Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Background: Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician’s sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers’ willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. Case Study: A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. Discussion: When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

Comparative quality of life in patients randomized contemporaneously to docetaxel or abiraterone in the STAMPEDE trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Hannah L. Rush ◽  
Adrian David Cook ◽  
Christopher D. Brawley ◽  
Laura Murphy ◽  
Archie Macnair ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Repeated Measures ◽  
Treatment Options ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Clinical Parameter ◽  
Cross Sectional ◽  
Multi Stage ◽  
Eortc Qlq

14 Background: Docetaxel (DOC) and abiraterone (ABI) both improve overall survival (OS) in men with locally advanced or metastatic hormone-sensitive prostate cancer (HSPC) but no head to head trials compare the 2 agents. STAMPEDE, a multi-arm multi-stage platform trial, recruited patients (pts) to treatments including DOC or ABI between Nov-11 and Mar-13. There was no evidence OS differed between DOC or ABI, thus quality of life (QOL) may increasingly inform treatment options. Methods: QOL scores were analysed in pts contemporaneously randomised to receive DOC or ABI, in addition to standard of care treatment. Self-assessment QOL questionnaires EORTC QLQ C30 and PR25 were completed during treatment and follow-up. These analyses focus on average global QOL over the first 2 years after randomisation, using repeated measures analysis, plus cross-sectional analyses at 3, 6, 12 and 24 months. A score difference of ≥4 points was pre-defined as clinically meaningful. Results: 173 men randomised to DOC and 342 men randomised to ABI participated in the QOL sub-study and contributed to this analysis. Baseline characteristics and proportion of missing data were similar between groups. Baseline global QOL scores were similar (mean (sd): DOC 77.8 (20) and ABI 78.0 (19.3)). Average global QOL over 2 years was higher in pts randomised to ABI than DOC, although the difference was statistically significant it did not meet the pre-defined clinical parameter (+3.9, 95%CI 0.6 to 7.1, p=0.021). Cross-sectional analyses showed clinically meaningful superior QOL in the ABI group at 3 and 6 months (+6.6, 95%CI 2.6 to 10.7, p=0.001; +8.0, 95%CI 3.6 to 12.3, p<0.001), but not at 1 or 2 years (+1.3, 95%CI -3.0 to 5.6, p=0.545; +4.5, 95%CI -0.25 to 9.2, p=0.063). An exploratory analysis indicated average QOL for pts with metastatic disease (n=207) was better in the ABI group (+4.44, 95%CI 0.2 to 8.6, p=0.036). Conclusion: Global QOL was significantly higher in the first 2 years of treatment for the ABI group compared to the DOC group, though did not meet the pre-defined clinically meaningful threshold. The majority of difference was seen in the first year of treatment. This should be considered when discussing treatment options with pts. Clinical trial information: NCT00268476.

scholarly journals What we learn from randomized trials in rectal cancer and what we can trust

2014 ◽  
Vol 61 (2) ◽  
pp. 9-16
Author(s):  
Vincenzo Valentini ◽  
Francesco Cellini
Keyword(s):  
Rectal Cancer ◽  
Randomized Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Integrated Treatment ◽  
Treatment Schedule ◽  
Optimal Outcome ◽  
Progressive Development ◽  
Rectal Cancers

Results of the management of rectal cancer have enormously improved over the last almost forty years, by the progressive development of new integrated treatment options. nevertheless an optimization of the results is needed to raise the still sub-optimal outcome in terms of survival. several national and international guidelines address the best treatment choice overall evaluating the evidence basis available from literature. Still a certain degree of disagreement is present, particularly about the preferable preoperative rt treatment schedule. randomized trials represent the main landmark and most important tool for the scientific scenario: defining a potentially established standard of care, or suggesting the more promising approach to focus the re- search into, thus orienting the efforts of clinicians and researchers. This manuscript will mainly focus on the evidences derived from randomized clinical trial describing the main issues about the multimodal integrated treatment for rectal cancers. It will focus on both locally advanced (LA)/primary unresectable (UR), and resectable rectal cancers; some non-randomized trials of relevant the dissertation will also be mentioned.

The PLATON pilot-study “Platform for analyzing targetable tumor mutations”: A PLATON network study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS6598-TPS6598
Author(s):  
Arndt Vogel ◽  
Bianca Zäpf ◽  
Thorsten Oliver Goetze ◽  
Benedikt Westphalen ◽  
Lothar Müller ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pilot Study ◽  
Web Application ◽  
Treatment Options ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Molecular Profile ◽  
Curative Therapy ◽  
Esophagogastric Cancer ◽  
Study Sites

TPS6598 Background: PLATON Network is designed as a platform to improve personalized therapy based on genomic profiles in gastrointestinal cancer patients. PLATON’s study-design focuses on patient’s molecular profiling and will provide a network web application for interlinking PLATON investigators which integrates information of the participating centers, their patients, the molecular profiles and available clinical trials at PLATON`s study-sites. Methods: The PLATON Network is designed as a permanent open, multicenter, prospective, cohort study with biobanking, with a shared platform infrastructure for associated sub-studies. In a first approach the PLATON Network enrolls within its pilot-study 200 patients in Germany of both sexes and ages over 18 at 40 study sites (NCT04484636) with signed informed consent. All patients of the pilot-study are diagnosed with hepatocellular cancer (HCC), intra- and extrahepatic cholangiocellular carcinoma (CCA), gallbladder carcinoma (GBCA), pancreatic cancer (PDCA) or esophagogastric cancer (EC/GC). At the time of enrolment, patients are within their first-line therapy and no local curative therapy is available. Molecular profiling will be performed with the Foundation Medicine Assays FoundationOne CDx and FoundationOne Liquid CDx. Investigators may use the platform for searching clinical trials matching the individual molecular profile of their patients or may identify a patient, who may be eligible for a study or other treatment options available at the corresponding centers of the PLATON network. The interactive network web application will comprise a dashboard and a moderated chat room to interact for example in a virtual Molecular Tumor Board. The first patient was included on the 25th of November 2020. Up to 12th of February 2021, a total of 36 patients HCC (N = 1), CCA (N = 6), PDCA (N = 12), GBCA (N = 0) and EC/GC (N = 16) were enrolled at 11 study-sites and the results of 29 genetic analyses were completed. All cohorts of the pilot-study are open for recruitments up to a maximum of 40 individuals per diagnostic group. Clinical trial information: NCT04484636.

scholarly journals Consensus Report of the National Cancer Institute Clinical Trials Planning Meeting on Pancreas Cancer Treatment

2009 ◽  
Vol 27 (33) ◽  
pp. 5660-5669 ◽  
Author(s):  
Philip A. Philip ◽  
Margaret Mooney ◽  
Deborah Jaffe ◽  
Gail Eckhardt ◽  
Malcolm Moore ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Predictive Biomarkers ◽  
Steering Committee ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Phase Ii Studies ◽  
Planning Meeting

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.

scholarly journals Update on the Treatment of Metastatic Urothelial Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Nedal Bukhari ◽  
Humaid O. Al-Shamsi ◽  
Faisal Azam
Keyword(s):  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Unfit Patients ◽  
Review Reports ◽  
First Line Treatment

Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review reports key findings from the clinical trials especially highlighting the importance of PD-1 and PD-L1 inhibitors in the treatment of bladder/urothelial carcinomas.

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