scholarly journals CDK4/6 Inhibitors in Melanoma: A Comprehensive Review

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1334
Author(s):  
Mattia Garutti ◽  
Giada Targato ◽  
Silvia Buriolla ◽  
Lorenza Palmero ◽  
Alessandro Marco Minisini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Drug Development ◽  
Metastatic Melanoma ◽  
Genetic Background ◽  
Preliminary Evidence ◽  
Active Compounds ◽  
Comprehensive Review ◽  
Mek Inhibitors ◽  
Recent Advances

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.

Phase 0 Clinical Trials in Cancer Drug Development: From FDA Guidance to Clinical Practice

2007 ◽  
Vol 7 (6) ◽  
pp. 325-334 ◽  
Author(s):  
R. Kinders ◽  
R. E. Parchment ◽  
J. Ji ◽  
S. Kummar ◽  
A. J. Murgo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Drug Development ◽  
Cancer Drug ◽  
Fda Guidance ◽  
Phase 0

Dealing with Ethical Issues in Clinical Trials: The ussr in the Global Context

2021 ◽  
pp. 1-15
Author(s):  
Pavel Vasilyev ◽  
Alexander Petrenko ◽  
Veronika Tayukina
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Drug Development ◽  
Ethical Issues ◽  
Free Market ◽  
Real Life ◽  
Scientific Research ◽  
Experimental Conditions ◽  
Double Blind ◽  
Soviet Model

Abstract This paper discusses several ethical issues related to clinical trials within the Soviet system of drug development and testing, which reflected larger ideological principles of healthcare organization in the ussr, with its focus on eradicating market elements from drug development. The centralized state-controlled system was thought to combat such drawbacks of free-market drug development as high prices and aggressive advertising; also to discourage the duplication of research by numerous independent actors that was perceived to be common in capitalist countries. Another significant ethical issue was the Soviet emphasis on the unity of scientific research and clinical treatment. Their strict separation, introduced to support normative standards defined by the U.S. pharmaceutical drug testing system, was rejected in the ussr where knowledge of new treatment options came from treatment practice, not laboratory-like experimental conditions of randomized controlled double-blind trials. The Soviet design was closer to so-called ‘pragmatic trials’ that focus on solving ‘real-life’ problems in clinical practice. Not all ethical problems were successfully addressed in the Soviet model, where there were always significant gaps between neatly postulated theory and messy clinical practice. The unity of scientific research and clinical practice was difficult to achieve. Archival research shows potential ethical issues related to geographic disparities in carrying out clinical trials, and the importance of personal and informal connections in the Soviet model.

Review: Microvascular complications: evaluation and monitoring relevance to clinical practice, clinical trials, and drug development

2007 ◽  
Vol 7 (4) ◽  
pp. 166-171 ◽  
Author(s):  
Adam Greenstein ◽  
Mitra Tavakoli ◽  
Moaz Mojaddidi ◽  
Ahmed Al-Sunni ◽  
Glenn Matfin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Drug Development ◽  
Microvascular Complications ◽  
Evaluation And Monitoring

scholarly journals Recent Advances in Experimental Dendritic Cell Vaccines for Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ivan Y. Filin ◽  
Kristina V. Kitaeva ◽  
Catrin S. Rutland ◽  
Albert A. Rizvanov ◽  
Valeriya V. Solovyeva
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Clinical Practice ◽  
Dendritic Cell ◽  
Therapeutic Vaccines ◽  
New Approaches ◽  
Recent Advances ◽  
Dc Vaccine ◽  
Oncological Diseases ◽  
Dc Vaccines

The development of immunotherapeutic methods for the treatment of oncological diseases have made it possible to improve the effectiveness of standard therapies. There was no breakthrough after first using of personalized therapeutic vaccines based on dendritic cells in clinical practice. A deeper study of the biology of dendritic cells, as well as the use of new approaches and agents for antigenic work, have made it possible to expand the field of application of dendritic cell (DC) vaccines and improve the indicators of cancer patients. In addition, the low toxicity of DC vaccines in clinical trials makes it possible to use promising predictions of their applicability in wider clinical practice. This review examines new approaches and recent advances of the DC vaccine in clinical trials.

scholarly journals Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab – real-world experience

2020 ◽  
Vol 54 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Nezka Hribernik ◽  
Marko Boc ◽  
Janja Ocvirk ◽  
Jasna Knez-Arbeiter ◽  
Tanja Mesti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Real World ◽  
Hospital Data ◽  
Real World Data ◽  
Treatment Naïve ◽  
Melanoma Patients ◽  
Metastatic Involvement

AbstractBackgroundBased on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials.Patients and methodsThis observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019.ResultsThe estimated median overall survival (OS) was 25.1 months (95% CI, 14.6–35.6) and the median progression-free survival (PFS) was 10.7 months (95% CI, 5.9–15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3–4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment.ConclusionsOur real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.

Controlling Hypertension and Stroke Prevention – From Guideline to Clinical Practice

2011 ◽  
Vol 3 (1) ◽  
pp. 30
Author(s):  
Anding Xu ◽  
Zefeng Tan ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Stroke Prevention ◽  
Modifiable Risk Factors ◽  
Cerebrovascular Events

Hypertension is the most important of the prevalent and modifiable risk factors for stroke. Based on evidence, blood pressure (BP) lowering is recommended in guidelines for the prevention of stroke. However, there are still some uncertainties in the guidelines for controlling BP and preventing stroke in patients with previous cerebrovascular events, such as the goal BP, who to treat and which class of BP-lowering drugs to use. This article discusses these questions by reviewing guidelines and corresponding clinical trials, with the aim of reducing the gap between guidelines and clinical practice.

ANTIBODY-DRUG CONJUGATES FOR TARGETED CANCER THERAPY

2019 ◽  
Vol 65 (6) ◽  
pp. 777-784
Author(s):  
David Korman
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Gemtuzumab Ozogamicin ◽  
Brentuximab Vedotin ◽  
Cytostatic Agent ◽  
Cytostatic Agents ◽  
Drug Conjugates ◽  
Natural Substances ◽  
Intracellular Release ◽  
High Antitumor Activity

Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

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