scholarly journals Clinical Trials in Metastatic Uveal Melanoma: Current Status

2020 ◽  
Vol 6 (6) ◽  
pp. 381-387
Author(s):  
Tamara A. Sussman ◽  
Pauline Funchain ◽  
Arun Singh
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Uveal Melanoma ◽  
Oncolytic Virus ◽  
Survival Rates ◽  
Standard Of Care ◽  
Therapeutic Benefit ◽  
Review Article ◽  
Current Status ◽  
Melanoma Prognosis

<b><i>Background:</i></b> Uveal melanoma is a rare subtype of melanoma. Prognosis and survival rates for patients with metastatic uveal melanoma remain poor. No current FDA-approved standard of care therapy is available for patients with metastatic uveal melanoma. Thus, clinical trials are essential for the development of new therapies and to provide patients hope for improved survival and outcomes. <b><i>Summary:</i></b> In this article, we review clinical trials identified on the database https://clinicaltrials.gov that are open and enrolling patients with metastatic uveal melanoma as of November 26, 2019. This search produced 17 active trials involving liver-directed therapy, CNS-directed therapy, and systemic therapy with immunotherapy, targeted therapy, or oncolytic virus therapy. Here, we discuss liver and CNS-directed therapy as well as systemic targeted therapy and oncolytic virus therapy. Immunotherapy clinical trials are discussed in a companion review article by Dr. Marlana Orloff. <b><i>Key Messages:</i></b> Various novel therapeutic targets and immunomodulatory approaches are on the horizon for patients with metastatic uveal melanoma and may yield incremental therapeutic benefit. Selecting a clinical trial must be individualized and made jointly with the patient and his/her oncologist.

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 Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5216
Author(s):  
Justus Körfer ◽  
Florian Lordick ◽  
Ulrich T. Hacker
Keyword(s):  
Gastric Cancer ◽  
Targeted Therapy ◽  
Molecular Characterization ◽  
Gastroesophageal Junction ◽  
Standard Of Care ◽  
Metastatic Gastric Cancer ◽  
Point Of View ◽  
Current Status ◽  
Molecular Alterations ◽  
Definition Of

Gastric cancer is a leading cause of cancer death worldwide. Systemic treatment comprising chemotherapy and targeted therapy is the standard of care in advanced/metastatic gastric cancer. Comprehensive molecular characterization of gastric adenocarcinomas by the TCGA Consortium and ACRG has resulted in the definition of distinct molecular subtypes. These efforts have in parallel built a basis for the development of novel molecularly stratified treatment approaches. Based on this molecular characterization, an increasing number of specific genomic alterations can potentially serve as treatment targets. Consequently, the development of promising compounds is ongoing. In this review, key molecular alterations in gastric and gastroesophageal junction cancers will be addressed. Finally, the current status of the translation of targeted therapy towards clinical applications will be reviewed.

scholarly journals Current status of therapeutic approaches and vaccines for SARS-CoV-2

2021 ◽  
Author(s):  
Braira Wahid ◽  
Anam Amir ◽  
Ayesha Ameen ◽  
Muhammad Idrees
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Review Article ◽  
Experimental Designs ◽  
Current Status ◽  
Therapeutic Approaches ◽  
Efficacious Treatment ◽  
Rapid Pace ◽  
Global Health Challenge

SARS-CoV-2, declared a pandemic in March 2020, is the current global health challenge. The global bioburden of this virus is increasing at a rapid pace. Many antiviral drugs and vaccines have been registered for clinical trials because of their inhibitory activity observed in vitro. Currently, five types of vaccines have successfully passed Phase IV clinical trial and are being administered in populations worldwide. A plethora of experimental designs have been proposed worldwide in order to find a safe and efficacious treatment option. Therefore, it is necessary to provide baseline data and information to clinicians and researchers so that they can review the current status of therapeutics and efficacy of already developed vaccines. This review article summarizes all therapeutic options that may help to combat SARS-CoV-2.

scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

scholarly journals Systemic treatment options for advanced biliary tract carcinoma

2020 ◽  
Vol 55 (10) ◽  
pp. 944-957
Author(s):  
Changqing Xie ◽  
Nicole A. McGrath ◽  
Cecilia Monge Bonilla ◽  
Jianyang Fu
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Biliary Tract ◽  
Treatment Options ◽  
Single Agent ◽  
Current Status ◽  
Dna Mismatch ◽  
First Line Therapy ◽  
Molecular Landscape ◽  
Line Setting

Abstract Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.

scholarly journals Photodynamic therapy in the treatment of intracranial gliomas: A review of current practice and considerations for future clinical directions

2015 ◽  
Vol 08 (01) ◽  
pp. 1530005 ◽  
Author(s):  
Carl J. Fisher ◽  
Lothar Lilge
Keyword(s):  
Clinical Trials ◽  
Photodynamic Therapy ◽  
Survival Time ◽  
Malignant Gliomas ◽  
Survival Rates ◽  
Standard Of Care ◽  
Therapeutic Index ◽  
Current Standard ◽  
Significant Survival ◽  
Tumor Volume Reduction

Invasive grade III and IV malignant gliomas remain difficult to treat with a typical survival time post-diagnosis hovering around 16 months with only minor extension thereof seen in the past decade, whereas some improvements have been obtained towards five-year survival rates for which completeness of resection is a prerequisite. Optical techniques such as fluorescence guided resection (FGR) and photodynamic therapy (PDT) are promising adjuvant techniques to increase the tumor volume reduction fraction. PDT has been used in combination with surgical resection or alternatively as standalone treatment strategy with some success in extending the median survival time of patients compared to surgery alone and the current standard of care. This document reviews the outcome of past clinical trials and highlights the general shift in PDT therapeutic approaches. It also looks at the current approaches for interstitial PDT and research options into increasing PDT's glioma treatment efficacy through exploiting both physical and biological-based approaches to maximize PDT selectivity and therapeutic index, particularly in brain adjacent to tumor (BAT). Potential reasons for failing to demonstrate a significant survival advantage in prior PDT clinical trials will become evident in light of the improved understanding of glioma biology and PDT dosimetry.

scholarly journals Current status of clinical trials assessing oncolytic virus therapy for urological cancers

2017 ◽  
Vol 24 (5) ◽  
pp. 342-351 ◽  
Author(s):  
Satoru Taguchi ◽  
Hiroshi Fukuhara ◽  
Yukio Homma ◽  
Tomoki Todo
Keyword(s):  
Clinical Trials ◽  
Oncolytic Virus ◽  
Current Status ◽  
Urological Cancers

scholarly journals Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1007 ◽  
Author(s):  
Anouk Jochems ◽  
Monique K. van der Kooij ◽  
Marta Fiocco ◽  
Maartje G. Schouwenburg ◽  
Maureen J. Aarts ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Real Life ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Lactate Dehydrogenase Level ◽  
Stage Iv Disease ◽  
Melanoma Treatment

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

scholarly journals Corticosteroids for Severe Coronavirus Disease 2019: High Time for High Dose Clinical Trials?

2021 ◽  
Author(s):  
A. Arturo Leis ◽  
Joseph L. Verheijde ◽  
Parminder J.S. Vig ◽  
Dobrivoje S. Stokic
Keyword(s):  
Clinical Trials ◽  
Critically Ill ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Pulse Therapy ◽  
Therapeutic Benefit ◽  
Lessons Learned ◽  
High Dose ◽  
Short Period ◽  
Need To Evaluate

Over 3 million deaths into the COVID-19 pandemic, low dose corticosteroids are still the chief therapeutic intervention to decrease mortality in critically ill COVID-19 patients. However, the persistently high mortality rate (approximately 30%) and the global surge in cases in 2021 associated with new more contagious variants of SARS-CoV-2 underscore the urgent need to evaluate whether the current corticosteroid regimens achieve the best possible outcomes. Our review of clinical, virological, and immunological data suggest that corticosteroids reduce COVID-19 mortality more when initiated in the second or third weeks after symptom onset, after viral infectivity has waned and SARS-CoV-2 immunopathology is maximal. At this time, clinical deterioration is driven by aberrant hyperinflammation. To counteract the hyperinflammation, we present credible arguments that high dose corticosteroids, defined in this Perspective as intravenous (i.v.) methylprednisolone 500-1000 mg/day for 3-7 days or the equivalent doses of other corticosteroids, can be administered with little or no risk of worsening viral replication and with expected benefits that greatly outweigh potential harm. Since the 1970s, the strategy of administering supraphysiologic doses of i.v. methylprednisolone (termed ‘pulse’ therapy) over a short period to enhance therapeutic benefit while decreasing harmful effects has become an accepted standard of care to effectively suppress inflammation in many autoimmune and immune-mediated disorders. It is particularly useful in conditions requiring rapid immunosuppression and anti-inflammatory effect and has recently been used to control inflammation in SARS-CoV-2 related complications, including multisystem inflammatory syndrome in children (MIS-C) and organizing pneumonia. In aggregate, awareness of the need for more aggressive immunosuppression and lessons learned over a half-century from the successful treatment of various inflammatory disorders, provide a sound scientific and ethics rationale for expeditiously conducting high dose corticosteroid randomized clinical trials (RCTs) in critically ill patients with COVID-19.

scholarly journals Treatment of uveal melanoma: where are we now?

2018 ◽  
Vol 10 ◽  
pp. 175883401875717 ◽  
Author(s):  
Jessica Yang ◽  
Daniel K. Manson ◽  
Brian P. Marr ◽  
Richard D. Carvajal
Keyword(s):  
Targeted Therapy ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Treatment Strategies ◽  
Current Status ◽  
Primary Therapy ◽  
Disease Outcomes ◽  
Unique Biology ◽  
Disease Biology ◽  
Metastatic Setting

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

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