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Targeted Oncology

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https://www.readbyqxmd.com/read/28361451/long-term-duration-of-first-line-axitinib-treatment-in-advanced-renal-cell-carcinoma
#1
Brian I Rini, Victor Gruenwald, Eric Jonasch, Mayer N Fishman, Yoshihiko Tomita, M Dror Michaelson, Jamal Tarazi, Laura Cisar, Subramanian Hariharan, Angel H Bair, Brad Rosbrook, Thomas E Hutson
OBJECTIVE: We conducted a retrospective analysis of two clinical trials in treatment-naïve patients (n = 402) with advanced renal cell carcinoma (RCC) treated with axitinib. Our objective was to compare duration of treatment (DT) and clinical outcome in patients who achieved DT >18 months (longer DT) versus ≤18 months (shorter DT). PATIENTS AND METHODS: DT, objective response rate (ORR), tumor shrinkage, and overall survival (OS) were summarized for patients with longer and shorter DT...
March 30, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28357727/a-phase-ib-study-of-the-dual-pi3k-mtor-inhibitor-dactolisib-bez235-combined-with-everolimus-in-patients-with-advanced-solid-malignancies
#2
Trisha M Wise-Draper, Ganesh Moorthy, Mohamad A Salkeni, Nagla Abdel Karim, Hala Elnakat Thomas, Carol A Mercer, M Shalaan Beg, Sue O'Gara, Olugbenga Olowokure, Hassana Fathallah, Sara C Kozma, George Thomas, Olivier Rixe, Pankaj Desai, John C Morris
BACKGROUND: The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model. OBJECTIVE: To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed. PATIENTS AND METHODS: BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2...
March 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28353074/gemcitabine-in-combination-with-a-second-cytotoxic-agent-in-the-first-line-treatment-of-locally-advanced-or-metastatic-pancreatic-cancer-a-systematic-review-and-meta-analysis
#3
REVIEW
Xiu-Wei Zhang, Yu-Xiang Ma, Yang Sun, Yu-Bo Cao, Qin Li, Chong-An Xu
BACKGROUND: It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC). OBJECTIVE: The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC...
March 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28353073/erratum-to-ongoing-response-in-braf-v600e-mutant-melanoma-after-cessation-of-intermittent-vemurafenib-therapy-a-case-report
#4
Andrew J Dooley, Avinash Gupta, Mark R Middleton
No abstract text is available yet for this article.
March 28, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28324270/obinutuzumab-a-review-in-rituximab-refractory-or-relapsed-follicular-lymphoma
#5
REVIEW
Sohita Dhillon
Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL)...
March 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28299600/sorafenib-a-review-in-hepatocellular-carcinoma
#6
REVIEW
Gillian M Keating
Sorafenib (Nexavar(®)) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall survival (OS) and time to radiological progression (TTP) with sorafenib 400 mg twice daily than with placebo, with no significant between-group difference in the median time to symptomatic progression (TTSP)...
March 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28281220/the-multifaceted-roles-of-b-cells-in-solid-tumors-emerging-treatment-opportunities
#7
Nicole J Flynn, Rajasekharan Somasundaram, Kimberly M Arnold, Jennifer Sims-Mourtada
The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a variety of solid tumors, including breast, ovarian, prostate, melanoma, and colorectal cancer. The function of B cells in solid tumors is controversial, with many studies reporting a pro-tumor effect, while other studies demonstrate a role for B cells in the anti-tumor immune response...
March 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#8
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28138797/exploiting-micrornas-as-cancer-therapeutics
#9
Tamsin Robb, Glen Reid, Cherie Blenkiron
miRNAs are a well-studied class of non-coding RNAs, predominantly functioning to down-regulate gene expression from messenger RNA (mRNA) in a targeted manner by binding to complementary sequence on the target mRNA. Many miRNAs have been linked to the development of hallmarks of cancer. miRNAs represent valuable therapeutic targets to exploit in the search for novel cancer treatments, due to their ubiquitous expression and their ability to tightly regulate the gene expression of a whole host of genes and pathways in a single hit...
January 30, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28255845/anti-pd-l1-atezolizumab-induced-autoimmune-diabetes-a-case-report-and-review-of-the-literature
#10
REVIEW
Laura Hickmott, Hugo De La Peña, Helen Turner, Fathelrahman Ahmed, Andrew Protheroe, Ashley Grossman, Avinash Gupta
Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28243959/mirnas-as-biomarkers-and-therapeutic-targets-in-non-small-cell-lung-cancer-current-perspectives
#11
Mateusz Florczuk, Adam Szpechcinski, Joanna Chorostowska-Wynimko
Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as non-small cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level. Deregulation of miRNA activity results in the loss of homeostasis and the development of a number of pathologies, including lung cancer...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28120215/erratum-to-a-combination-of-the-telomerase-inhibitor-bibr1532-and-paclitaxel-synergistically-inhibit-cell-proliferation-in-breast-cancer-cell-lines
#12
Yi Shi, Lin Sun, Ge Chen, Dongyan Zheng, Li Li, Wanguo Wei
No abstract text is available yet for this article.
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28000147/erratum-to-aflibercept-a-new-way-to-target-angiogenesis-in-the-second-line-treatment-of-metastatic-colorectal-cancer-mcrc
#13
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
No abstract text is available yet for this article.
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#14
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27975152/phase-i-ii-study-of-refametinib-bay-86-9766-in-combination-with-gemcitabine-in-advanced-pancreatic-cancer
#15
Jean-Luc Van Laethem, Hanno Riess, Jacek Jassem, Michael Haas, Uwe M Martens, Colin Weekes, Marc Peeters, Paul Ross, John Bridgewater, Bohuslav Melichar, Stefano Cascinu, Piotr Saramak, Patrick Michl, David Van Brummelen, Alberto Zaniboni, Wollf Schmiegel, Svein Dueland, Marius Giurescu, Vittorio L Garosi, Katrin Roth, Anke Schulz, Henrik Seidel, Prabhu Rajagopalan, Michael Teufel, Barrett H Childs
BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27844272/resistance-to-targeted-therapies-in-renal-cancer-the-importance-of-changing-the-mechanism-of-action
#16
I Duran, J Lambea, P Maroto, J L González-Larriba, Luis Flores, S Granados-Principal, M Graupera, B Sáez, A Vivancos, O Casanovas
Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27796762/new-biomarkers-for-selecting-the-best-therapy-regimens-in-metastatic-castration-resistant-prostate-cancer
#17
Isabel Heidegger, Axel Heidenreich, David Pfister
Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27638381/regorafenib-in-the-real-life-clinical-practice-data-from-the-czech-registry
#18
Katerina Kopeckova, Tomas Buchler, Zbynek Bortlicek, Karel Hejduk, Renata Chloupkova, Bohuslav Melichar, Petra Pokorna, Jiri Tomasek, Zdenek Linke, Lubos Petruzelka, Igor Kiss, Jana Prausova
OBJECTIVE: To describe the use of regorafenib for the treatment of metastatic colorectal cancer (mCRC) in clinical practice in the Czech Republic, and to describe the clinical outcomes of patients in terms of safety and survival. PATIENTS AND METHODS: The data of patients treated with regorafenib were extracted from the national CORECT registry. The CORECT registry is a non-interventional post-marketing database, gathering information about patients with CRC and treated with targeted agents...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27573024/the-unexpected-roles-of-aurora-a-kinase-in-gliobastoma-recurrences
#19
Estelle Willems, Arnaud Lombard, Matthias Dedobbeleer, Nicolas Goffart, Bernard Rogister
The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We urgently need new therapies to specifically address these deadly relapses. A major advance in the understanding of GBM recurrence is the identification of GBM-Initiating Cells (GIC), characterized by their abilities for self-renewal, multilineage differentiation, and proliferation. It appears that these features of GIC could be modulated by the mitotic kinase Aurora A (AurA)...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27538584/response-to-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-the-rare-epidermal-growth-factor-receptor-mutation-s768i-a-retrospective-analysis-and-literature-review
#20
Xiaoli Zhu, Qianming Bai, Yongming Lu, Peng Qi, Jianhui Ding, Jialei Wang, Xiaoyan Zhou
BACKGROUND: The rare epidermal growth factor receptor (EGFR) mutation S768I has only been reported sporadically in patients with lung adenocarcinoma (AC). OBJECTIVE: This study aimed to investigate the prevalence of the S768I mutation in Chinese patients with lung AC and to retrospectively analyze the response of S768I mutants to tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: A total of 6698 tissue specimens of lung AC were collected from the Department of Pathology of Shanghai Cancer Center of Fudan University between 2013 and 2015 and screened for EGFR mutations...
February 2017: Targeted Oncology
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