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Clinical trial metastatic melanoma

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https://www.readbyqxmd.com/read/29659371/real-world-use-safety-and-survival-of-ipilimumab-in-metastatic-cutaneous-melanoma-in-the-netherlands
#1
Anouk Jochems, Brenda Leeneman, Margreet G Franken, Maartje G Schouwenburg, Maureen J B Aarts, Alexander C J van Akkooi, Franchette W P J van den Berkmortel, Alfonsus J M van den Eertwegh, Gerard Groenewegen, Jan Willem B de Groot, John B A G Haanen, Geke A P Hospers, Ellen Kapiteijn, Rutger H Koornstra, Wim H J Kruit, Marieke W J Louwman, Djura Piersma, Rozemarijn S van Rijn, Albert J Ten Tije, Gerard Vreugdenhil, Michel W J M Wouters, Carin A Uyl-de Groot, Koos J M van der Hoeven
Phase III trials with ipilimumab showed an improved survival in patients with metastatic melanoma. We evaluated the use and safety of ipilimumab, and the survival of all patients with metastatic cutaneous melanoma (N=807) receiving ipilimumab in real-world clinical practice in The Netherlands using data from the Dutch Melanoma Treatment Registry. Patients who were registered between July 2012 and July 2015 were included and analyzed according to their treatment status: treatment-naive (N=344) versus previously-treated (N=463)...
April 13, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29650221/lymph-node-dissection-in-patients-with-melanoma-and-sentinel-lymph-node-metastasis-an-updated-evidence-based-decision-algorithm
#2
D Moreno-Ramírez, A Boada, L Ferrándiz, E Samaniego, G Carretero, E Nagore, P Redondo, P Ortiz-Romero, J Malvehy, R Botella-Estrada
Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting...
April 9, 2018: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29628796/immunotherapy-of-melanoma
#3
Iwona Lugowska, Pawel Teterycz, Piotr Rutkowski
The immunotherapy is currently changing the landscape of oncology. Nowadays the standard of care in metastatic or unresectable melanoma patients include immunomodulating modalities such as anti-PD-1 drugs (nivolumab, pembrolizumab) and anti-CTLA-4 antibody ipilimumab. The improvements of progression free survival and overall survival connected with those treatments were unprecedented and have been confirmed in stage III trials. The efficacy of immunotherapy in metastatic setting can be further upgraded in some groups of patients by combining both types of antibodies...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29628780/emerging-treatment-options-for-braf-mutant-colorectal-cancer
#4
Carling Ursem, Chloe E Atreya, Katherine Van Loon
The personalization of cancer care is rooted in the premise that there are subsets of patients with tumors harboring clinically relevant targets for patient-specific treatments. Colorectal cancer (CRC) is a disease that has historically been notable for its dearth of biomarkers that are predictive of response to targeted therapies. In recent years, BRAF V600E -mutated CRC has emerged as a distinct biologic entity, typically refractory to standard chemotherapy regimens approved for the treatment of metastatic CRC and associated with a dismal prognosis...
2018: Gastrointestinal Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29615812/structure-function-analysis-and-therapeutic-efficacy-of-antibodies-to-fungal-melanin-for-melanoma-radioimmunotherapy
#5
J D Nosanchuk, A Jeyakumar, A Ray, E Revskaya, Z Jiang, R A Bryan, K J H Allen, R Jiao, M E Malo, B L Gómez, A Morgenstern, F Bruchertseifer, D Rickles, G B Thornton, A Bowen, A Casadevall, E Dadachova
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188 Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29595366/dabrafenib-in-combination-with-trametinib-in-the-treatment-of-patients-with-braf-v600-positive-advanced-or-metastatic-non-small-cell-lung-cancer-clinical-evidence-and-experience
#6
Arjun Khunger, Monica Khunger, Vamsidhar Velcheti
Mutations in the BRAF oncogene are found in 2-4% of all non-small cell lung cancer (NSCLC) patients. The most common activating mutation present within the BRAF oncogene is associated with valine substitution for glutamate at position 600 (V600E) within the BRAF kinase. BRAF-targeted therapies are effective in patients with melanoma and NSCLC harboring BRAF V600E mutation. In both melanoma and NSCLC, dual inhibition of both BRAF and the downstream mitogen-activated protein kinase (MEK) improves response rates compared with BRAF inhibition alone...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29594244/combining-radiotherapy-and-ipilimumab-induces-clinically-relevant-radiation-induced-abscopal-effects-in-metastatic-melanoma-patients-a-systematic-review
#7
REVIEW
Rodolfo Chicas-Sett, Ignacio Morales-Orue, Delvys Rodriguez-Abreu, Pedro Lara-Jimenez
Background: In the last years, limited studies have described that radiotherapy could produce important distant responses in unirradiated sites, the so-called "abscopal effect". Recent evidence suggests that radiotherapy induces antigen release from tumor, in this way activating the immune system. However, radiotherapy alone is rarely enough to induce the systemic response requested for control of the metastases. With the advent of immunotherapy, the immune checkpoint inhibitors (ICI) have demonstrated impressive efficacy in various metastatic cancers...
February 2018: Clinical and Translational Radiation Oncology
https://www.readbyqxmd.com/read/29593889/immunotherapy-combination-strategies-non-chemotherapy-in-non-small-cell-lung-cancer
#8
REVIEW
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29575357/rasopathic-comedo-like-or-cystic-lesions-induced-by-vemurafenib-a-model-of-skin-lesions-similar-but-not-identical-to-those-induced-by-dioxins-madish
#9
G Kaya, N Saxer-Sekulic, A Kaya, O Sorg, A Boespflug, L Thomas, J H Saurat
BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible cross-talk between vemurafenib and dioxin pathways...
March 24, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29574334/immuno-oncology-in-head-and-neck-squamous-cell-cancers-news-from-clinical-trials-emerging-predictive-factors-and-unmet-needs
#10
REVIEW
Stefano Cavalieri, Licia Rivoltini, Cristiana Bergamini, Laura D Locati, Lisa Licitra, Paolo Bossi
According to the new determinants of cancer immunity, head and neck squamous cell cancer (HNSCC) has to be considered as an immunogenic tumor for the relatively high number of somatic mutations giving rise to neoantigens recognized by T cell. HNSCC develop at a significant rate despite the antitumoral immune response indicating the existence of effective escape mechanisms. The lack of antigen presentation or co-stimulatory molecules required and immunosuppressive phenomena established by the tumor or the host microenvironment impair immune-mediated recognition and cancer control...
March 20, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29569208/melanoma-and-immune-checkpoint-inhibitors
#11
REVIEW
Masutaka Furue, Takamichi Ito, Naoko Wada, Maiko Wada, Takafumi Kadono, Hiroshi Uchi
PURPOSE OF REVIEW: Prognosis of patients with advanced melanoma is dismal with a median overall survival of about 8 months and 5-year overall survival from a diagnosis of metastatic disease of roughly 10%. However, immune checkpoint inhibitors have brought indispensable benefits to melanoma patients. Here we will review the recent clinical efficacy and adverse events of immune checkpoint inhibitors for melanoma patients. RECENT FINDINGS: The immune checkpoint inhibitors increase confirmed objective response and prolong progression-free and overall survival of the afflicted patients in association with maintaining their quality of life...
March 23, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29563820/modeling-the-economic-outcomes-of-immuno-oncology-drugs-alternative-model-frameworks-to-capture-clinical-outcomes
#12
E J Gibson, N Begum, I Koblbauer, G Dranitsaris, D Liew, P McEwan, A A Tahami Monfared, Y Yuan, A Juarez-Garcia, D Tyas, M Lees
Background: Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. Materials and methods: This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy...
2018: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29552321/combined-vemurafenib-and-fotemustine-in-patients-with-braf-v600-melanoma-progressing-on-vemurafenib
#13
Paola Queirolo, Francesco Spagnolo, Virginia Picasso, Laura Spano, Enrica Tanda, Valeria Fontana, Laura Giorello, Domenico Franco Merlo, Ester Simeone, Antonio Maria Grimaldi, Marcello Curvietto, Michele Del Vecchio, Paolo Bruzzi, Paolo Antonio Ascierto
Background: BRAF inhibitor vemurafenib achieves high response rate and an improvement in survival in patients with BRAF-mutated metastatic melanoma. However, median progression-free survival is only 6.9 months in the phase 3 study. Retrospective analyses suggest that treatment with BRAF inhibitors beyond initial progression might be associated with improved overall survival. We aimed to prospectively investigate the activity of prolonged treatment with vemurafenib and the addition of fotemustine in patients with systemic progression on prior single-agent BRAF inhibitor...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29552014/autoantibodies-may-predict-immune-related-toxicity-results-from-a-phase-i-study-of-intralesional-bacillus-calmette-gu%C3%A3-rin-followed-by-ipilimumab-in-patients-with-advanced-metastatic-melanoma
#14
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29551128/prospects-of-gene-therapy-to-treat-melanoma
#15
Mitchell E Menezes, Sarmistha Talukdar, Stephen L Wechman, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher
The incidence of melanoma has continued to increase over the past 30 years. Hence, developing effective therapies to treat both primary and metastatic melanoma are essential. While advances in targeted therapy and immunotherapy have provided novel therapeutic options to treat melanoma, gene therapy may provide additional strategies for the treatment of metastatic melanoma clinically. This review focuses upon the challenges and opportunities that gene therapy provides for targeting melanoma. We begin with a discussion of the various gene therapy targets which are relevant to melanoma...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29551126/role-of-mda-7-il-24-a-multifunction-protein-in-human-diseases
#16
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29550466/a-spontaneous-metastatic-mathematical-model-in-mice-for-screening-anti-metastatic-agents
#17
Yao Li, Zhiqiang Yue, Hua Yu, Xiaojian Liu, Li Tao, Zhijie Zhu, Fangtian Fan, Cunsi Shen, Aiyun Wang, Wenxing Chen, Yin Lu
PURPOSE: A computational model based on clinical data from pancreatic cancer patients has been successfully created and used for predicting tumor sizes in primary and metastasis sites and survival time from kinetics of tumor cells, such as growth rate, metastasis rate and mutation rate, etc. Whether this computational model could be fitted or necessary modification of some parameters for fitting in mice is unknown. Here, we developed a computational model in mice for spontaneous metastasis to simulate the process of tumor metastasis based on the mathematical frameworks...
March 14, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29543704/three-antigen-loading-methods-in-dendritic-cell-vaccines-for-metastatic-melanoma
#18
Larisa J Geskin, James J Damiano, Christina C Patrone, Lisa H Butterfield, John M Kirkwood, Louis D Falo
In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery...
March 14, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29541385/targeting-the-cyclin-dependent-kinase-and-retinoblastoma-axis-overcomes-standard-of-care-resistance-in-braf-v600e-mutant-melanoma
#19
Antoneicka L Harris, Samantha E Lee, Louis K Dawson, Laura A Marlow, Brandy H Edenfield, William F Durham, Thomas J Flotte, Michael Thompson, Daniel L Small, Aidan J Synnott, Svetomir N Markovic, John A Copland
Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29534829/use-of-extracranial-radiation-therapy-in-metastatic-melanoma-patients-receiving-immunotherapy
#20
Prashant Gabani, Clifford G Robinson, George Ansstas, Tanner M Johanns, Jiayi Huang
PURPOSE: Explore the patterns of use of extracranial radiation therapy (RT) in metastatic melanoma patients receiving immunotherapy, its potential association with OS, the impact of the site and timing of RT on clinical outcomes when combined with immunotherapy. MATERIALS AND METHODS: Patients with extracranial metastatic melanoma who received immunotherapy with or without extracranial RT from 2004 to 2013 were obtained from the National Cancer Database. Multivariable Cox regression analysis was used to evaluate factors associated with overall survival (OS)...
March 10, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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