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Ryo Fujiwara, Mitsuhiro Narita, Susumu Kageyama, Akihiro Kawauchi, Takahisa Nakayama, Natsumi Nishi, Hiroyuki Sugihara, Yusaku Okada
A 67-year-old man presented at our hospital with severe edema on the left side of his neck, chest and brachial regions. He had a history of right radical nephrectomy due to renal cell carcinoma (RCC, clear cell subtype, stage II) 15 years earlier. Thereafter, metastases to the pancreatic tail and right lung, and left lung metastasis were removed at 8 years and 11 years, respectively, after the nephrectomy. Four years earlier, he had also undergone total gastrectomy for gastric carcinoma (poorly differentiated adenocarcinoma, stage IV) and subsequent maintenance chemotherapy for gastric carcinoma...
September 2016: Hinyokika Kiyo. Acta Urologica Japonica
Maria T Bourlon, Dexiang Gao, Sara Trigero, Julia E Clemons, Kathryn Breaker, Elaine T Lam, Thomas W Flaig
Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression-free-survival (PFS) is unknown. We aimed to characterize TKI-associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting...
October 19, 2016: Cancer Medicine
Roberto Iacovelli, Elena Verri, Maria Cossu Rocca, Gaetano Aurilio, Daniela Cullurà, Ottavio de Cobelli, Franco Nolè
Tyrosine kinase inhibitor-related toxicities have been reported to be predictive and/or prognostic factors in patients affected by metastatic renal cell carcinoma (mRCC). We aim to investigate the incidence of cumulative toxicity and its prognostic role in mRCC patients treated with sunitinib or pazopanib. mRCC patients treated with sunitinib or pazopanib at the European Institute of Oncology in Milan were reviewed for the incidence of adverse events. Cumulative toxicity was defined as the presence of more than one selected adverse event of any grade...
October 14, 2016: Anti-cancer Drugs
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
A Spek, B Szabados, B Ziegelmüller, C Stief, M D'Anastasi, M Staehler
OBJECTIVES: To evaluate the usage of different guidelines and to estimate the impact of changed recommendation in routine management, therapy and follow-up of patients with renal cell cancer (RCC). METHODS: An anonymous questionnaire was sent to 600 urologists in Germany. Twenty-seven percent of them were included in the analysis. The questions were about the practice setting, surgical and medical treatment of RCC, follow-up modalities, knowledge and usage of RCC guidelines...
October 18, 2016: Urologia Internationalis
M Herbrink, N de Vries, H Rosing, A D R Huitema, B Nuijen, J H M Schellens, J H Beijnen
BACKGROUND: A liquid chromatography/tandem mass spectrometry assay was developed to facilitate therapeutic drug monitoring (TDM) for 10 anticancer compounds (dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, sorafenib, sunitinib, and vemurafenib) and the active metabolite, N-desethyl-sunitinib. METHODS: The TDM assay is based on reversed-phase chromatography coupled with tandem mass spectrometry in the positive ion mode using multiple-reaction monitoring for analyte quantification...
October 5, 2016: Therapeutic Drug Monitoring
Jessica E Maxwell, Scott K Sherman, James R Howe
Pancreatic neuroendocrine tumors (PNET) are rare tumors, but have been increasing in incidence. Although typically thought of as indolent, more than half of patients present with metastatic disease. For many years, the only mutations commonly known in these tumors were those in the MEN1 gene. Recently, the genetics underlying PNETs have been further defined through exome sequencing. The most frequent alterations found in sporadic PNETs are in MEN1, DAXX/ATRX, and a variety of genes in the mTOR pathway. Confirmation of these mutations has prompted trials with a number of drugs active in these pathways, and two drugs were eventually approved in 2011-sunitinib and everolimus...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Michelangelo Fiorentino, Elisa Gruppioni, Francesco Massari, Francesca Giunchi, Annalisa Altimari, Chiara Ciccarese, Davide Bimbatti, Aldo Scarpa, Roberto Iacovelli, Camillo Porta, Sarhadi Virinder, Giampaolo Tortora, Walter Artibani, Riccardo Schiavina, Andrea Ardizzoni, Matteo Brunelli, Sakari Knuutila, Guido Martignoni
Renal cell cancer (RCC) is characterized by histological and molecular heterogeneity that may account for variable response to targeted therapies. We evaluated retrospectively with a next generation sequencing (NGS) approach using a pre-designed cancer panel the mutation burden of 32 lesions from 22 metastatic RCC patients treated with at least one tyrosine kinase or mTOR inhibitor. We identified mutations in the VHL, PTEN, JAK3, MET, ERBB4, APC, CDKN2A, FGFR3, EGFR, RB1, TP53 genes. Somatic alterations were correlated with response to therapy...
October 10, 2016: Oncotarget
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
October 13, 2016: JAMA Oncology
Letizia Canu, Silvia Pradella, Elena Rapizzi, Rossella Fucci, Andrea Valeri, Vittorio Briganti, Valentino Giachè, Gabriele Parenti, Tonino Ercolino, Massimo Mannelli
Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL...
October 10, 2016: Archives of Endocrinology and Metabolism
Hidenori Fujita, Akira Gomori, Yayoi Fujioka, Yuki Kataoka, Kenji Tanaka, Akihiro Hashimoto, Takamasa Suzuki, Kenjiro Ito, Tomonori Haruma, Hiromi Yamamoto-Yokoi, Naomoto Harada, Motomu Sakuragi, Nobuyuki Oda, Kenichi Matsuo, Masaki Inada, Kazuhiko Yonekura
Approximately 25-40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice...
2016: PloS One
Carmine D'Aniello, Maria G Vitale, Azzurra Farnesi, Lorenzo Calvetti, Maria M Laterza, Carla Cavaliere, Chiara Della Pepa, Vincenza Conteduca, Anna Crispo, Ferdinando De Vita, Francesco Grillone, Enrico Ricevuto, Michele De Tursi, Rocco De Vivo, Marilena Di Napoli, Sabrina C Cecere, Gelsomina Iovane, Alfonso Amore, Raffaele Piscitelli, Giuseppe Quarto, Salvatore Pisconti, Gennaro Ciliberto, Piera Maiolino, Paolo Muto, Sisto Perdonà, Massimiliano Berretta, Emanuele Naglieri, Luca Galli, Giacomo Cartenì, Ugo De Giorgi, Sandro Pignata, Gaetano Facchini, Sabrina Rossetti
Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint...
2016: Frontiers in Pharmacology
Ming Guo, Yunsong Cao, Jingzhe Yang, Jingfeng Zhang
PURPOSE: The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. MATERIALS AND METHODS: Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis...
October 2016: Journal of Cancer Research and Therapeutics
Lingling Chang, Ying An, Shuling Yang, Xiaosu Zhang
PURPOSE: A meta-analysis of published data was conducted to investigate the therapeutic effects in patients with renal cell carcinoma (RCC) who were receiving antiangiogenic drugs. METHODS: A computerized search through electronic databases, including PubMed (until February 2016), was performed to obtain eligible randomized controlled trials that compared the effectiveness of antiangiogenic with control groups (everolimus, placebo, and interferon [IFN] alfa) in patients with RCC...
October 2016: Journal of Cancer Research and Therapeutics
Jordi Remon, Nicolas Girard, Julien Mazieres, Eric Dansin, Eric Pichon, Laurent Greillier, Catherine Dubos, Colin R Lindsay, Benjamin Besse
No abstract text is available yet for this article.
October 6, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Brian I Rini, Arnulf Stenzl, Romauld Zdrojowy, Mikhail Kogan, Mikhail Shkolnik, Stephane Oudard, Steffen Weikert, Sergio Bracarda, Simon J Crabb, Jens Bedke, Joerg Ludwig, Dominik Maurer, Regina Mendrzyk, Claudia Wagner, Andrea Mahr, Jens Fritsche, Toni Weinschenk, Steffen Walter, Alexandra Kirner, Harpreet Singh-Jasuja, Carsten Reinhardt, Tim Eisen
BACKGROUND: In a phase 2 study in patients with metastatic renal cell carcinoma, overall survival was associated with T-cell responses against IMA901, a vaccine consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to determine the clinical effect of adding IMA901 to sunitinib, the standard first-line treatment in metastatic renal cell carcinoma with postulated favourable immunomodulatory effects. METHODS: The IMPRINT study is an open-label, randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries...
October 3, 2016: Lancet Oncology
Alain Ravaud, Robert J Motzer, Hardev S Pandha, Daniel J George, Allan J Pantuck, Anup Patel, Yen-Hwa Chang, Bernard Escudier, Frede Donskov, Ahmed Magheli, Giacomo Carteni, Brigitte Laguerre, Piotr Tomczak, Jan Breza, Paola Gerletti, Mariajose Lechuga, Xun Lin, Jean-Francois Martini, Krishnan Ramaswamy, Michelle Casey, Michael Staehler, Jean-Jacques Patard
Background Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. Methods In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal...
October 9, 2016: New England Journal of Medicine
Carlos H Barrios, Daniel Herchenhorn, Matías Chacón, Paula Cabrera-Galeana, Peter Sajben, Ke Zhang
BACKGROUND: Sunitinib is an approved treatment for metastatic renal cell carcinoma (mRCC). The safety profile and efficacy of sunitinib were confirmed in a global expanded access trial ( identifier: NCT00130897). This report presents a subanalysis of the final trial data from patients in Latin America. METHODS: Treatment-naïve or previously treated mRCC patients aged ≥18 years received oral sunitinib at a starting dose of 50 mg/day on a 4-weeks-on/2-weeks-off schedule...
2016: OncoTargets and Therapy
Steven S Yu, David I Quinn, Tanya B Dorff
Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016...
2016: OncoTargets and Therapy
Claudia Karnthaler-Benbakka, Diana Groza, Bettina Koblmüller, Alessio Terenzi, Katharina Holste, Melanie Haider, Dina Baier, Walter Berger, Petra Heffeter, Christian R Kowol, Bernhard K Keppler
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture...
October 5, 2016: ChemMedChem
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