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Lin Yang, Anna Alyasova, Dingwei Ye, Antonia Ridolfi, Luca Dezzani, Robert J Motzer
BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients...
February 17, 2018: BMC Cancer
Julia Kovacova, Alexandr Poprach, Tomas Buchler, William C Cho, Ondrej Slaby
Renal cell carcinoma (RCC) accounts for 2%-3% of all malignant tumours. The first-choice treatment in metastatic RCC (mRCC) patients is tyrosine kinase inhibitors (TKIs). Although TKIs may prolong survival of the treated patients who are not primary resistant, almost all of them will eventually develop secondary resistance to the treatment after a progression-free period. To predict treatment response, thus, we need efficient biomarkers for rational indication of TKIs in mRCC. MicroRNAs (miRNAs) not only play important roles in the pathogenesis of many cancers, including RCC but also have been shown to serve as promising diagnostic, prognostic and predictive biomarkers in various cancers...
February 16, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
Sung Han Kim, Kyung-Chae Jeong, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, Jinsoo Chung
We compared progression-free survival (PFS) and overall survival (OS) among 292 metastatic renal cell carcinoma (mRCC) patients either undergoing nephrectomy (Nx, 61.6%) or not (non-Nx, 38.4%), stratified according to the MSKCC and Heng risk models, treated with either immunotherapy (IT, 45.2%) or targeted therapy (TT, 54.8%) between 2000 and 2015. During the follow-up duration of 16.6 months, PFS/OS of the Nx (6.0/30 months) and non-Nx (3.0/6.0 months) groups were significantly different despite differences among baseline parameters (p < 0...
February 14, 2018: Scientific Reports
Dylan J Martini, Lana Hamieh, Rana R McKay, Lauren C Harshman, Raphael Brandao, Craig K Norton, John A Steinharter, Katherine M Krajewski, Xin Gao, Fabio A Schutz, Bradley McGregor, Dominick Bosse, Aly-Khan Lalani, Guillermo de Velasco, M Dror Michaelson, David F McDermott, Toni K Choueiri
The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAEs) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary end-point was time to progression from the date of treatment cessation (TTP)...
February 1, 2018: Cancer Immunology Research
Kriti Mittal, Lisa Derosa, Laurence Albiges, Laura Wood, Paul Elson, Timothy Gilligan, Jorge Garcia, Robert Dreicer, Bernard Escudier, Brian Rini
INTRODUCTION: Tyrosine kinase inhibitor (TKI) therapy in metastatic renal-cell carcinoma (mRCC) is noncurative and may be associated with significant toxicities. Some patients may receive treatment breaks as a result of TKI-related adverse effects or planned drug holidays. PATIENTS AND METHODS: In this retrospective study, mRCC patients who underwent drug holidays during TKI therapy at 2 different institutions were analyzed. A drug holiday was defined as a period of drug cessation for ≥ 3 months for reasons other than progressive disease...
January 4, 2018: Clinical Genitourinary Cancer
Mehmet Asim Bilen, Giselle Marie Almeida Dutcher, Yuan Liu, Deepak Ravindranathan, Haydn T Kissick, Bradley C Carthon, Omer Kucuk, Wayne B Harris, Viraj A Master
BACKGROUND: Biomarkers to guide treatment in metastatic renal-cell carcinoma (mRCC) are lacking. We aimed to investigate the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and outcome of patients with mRCC receiving nivolumab. PATIENTS AND METHODS: Through retrospective chart review, we identified 38 patients with mRCC treated with standard-of-care nivolumab between 2015 and 2016 at Winship Cancer Institute of Emory University. NLR was determined from complete blood count collected before starting treatment, and imaging was performed to assess progression...
January 4, 2018: Clinical Genitourinary Cancer
Frede Donskov, Niels Viggo Jensen, Torben Smidt-Hansen, Line Brøndum, Poul Geertsen
BACKGROUND: Interleukin-2 (IL2)-based immunotherapy is curative for a small subset of patients with metastatic renal-cell carcinoma (mRCC). Preclinical data suggests that bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has potential immunomodulatory effects by permitting efficient natural killer (NK) cell-mediated killing and by reverting immune suppression. PATIENT AND METHODS: We performed a randomized phase II study comparing IL2/IFN (interferon)/BEV with IL2/IFN in favourable/intermediate-risk mRCC patients...
February 2, 2018: Acta Oncologica
Kojiro Ohba, Yasuyoshi Miyata, Takuji Yasuda, Akihiro Asai, Kensuke Mitsunari, Tomohiro Matsuo, Yasushi Mochizuki, Noriko Matsunaga, Hideki Sakai
AIM: Sunitinib is a standard agent for metastatic renal cell carcinoma (mRCC). The standard schedule, 4 weeks-on followed by 2 weeks-off (4/2 schedule), often does not maintain an adequate dosage because of the severe adverse events (AEs). We compared the efficacy and safety of an alternative every other day (q.a.d.) dosing with that of the 4/2 schedule in mRCC patients. METHODS: Of the 55 Japanese patients, 32 and 23 were administered 4/2 (standard group) and q...
January 31, 2018: Asia-Pacific Journal of Clinical Oncology
John M Hudson, Colleen Bailey, Mostafa Atri, Greg Stanisz, Laurent Milot, Ross Williams, Alex Kiss, Peter N Burns, Georg A Bjarnason
OBJECTIVES: To identify dynamic contrast-enhanced (DCE) imaging parameters from MRI, CT and US that are prognostic and predictive in patients with metastatic renal cell cancer (mRCC) receiving sunitinib. METHODS: Thirty-four patients were monitored by DCE imaging on day 0 and 14 of the first course of sunitinib treatment. Additional scans were performed with DCE-US only (day 7 or 28 and 2 weeks after the treatment break). Perfusion parameters that demonstrated a significant correlation (Spearman p < 0...
January 30, 2018: European Radiology
Vadim S Koshkin, Pedro C Barata, Tian Zhang, Daniel J George, Michael B Atkins, William J Kelly, Nicholas J Vogelzang, Sumanta K Pal, JoAnn Hsu, Leonard J Appleman, Moshe C Ornstein, Timothy Gilligan, Petros Grivas, Jorge A Garcia, Brian I Rini
BACKGROUND: Nivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials. METHODS: Patients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1...
January 29, 2018: Journal for Immunotherapy of Cancer
Xiang Chen, Li Liu, Jiajun Wang, Zhiyuan Lin, Ying Xiong, Yang Qu, Zewei Wang, Yuanfeng Yang, Jianming Guo, Jiejie Xu
PURPOSE: CXCR1 signaling promotes tumor progression in various cancers, and clinical trial has proved efficacy of CXCR1 inhibitor in metastatic breast cancer. Therefore, we investigated the prognostic value of CXCR1 in patients with metastatic renal cell carcinoma (mRCC) receiving tyrosine kinase inhibitors (TKIs) therapy. MATERIALS AND METHODS: Patients treated with sunitinib or sorafenib were retrospectively enrolled (n = 111). CXCR1 expression was assessed by immunohistochemical staining of tissue microarrays of primary tumor, and its association with prognosis and therapeutic response were evaluated...
January 19, 2018: Urologic Oncology
Aly-Khan A Lalani, Wanling Xie, Dylan J Martini, John A Steinharter, Craig K Norton, Katherine M Krajewski, Audrey Duquette, Dominick Bossé, Joaquim Bellmunt, Eliezer M Van Allen, Bradley A McGregor, Chad J Creighton, Lauren C Harshman, Toni K Choueiri
BACKGROUND: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB. METHODS: We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA)...
January 22, 2018: Journal for Immunotherapy of Cancer
Javier González, Jeffrey J Gaynor, Mahmoud Alameddine, Manuel Esteban, Gaetano Ciancio
Surgery may set the basis for a potential cure or would provide the best achievable quality of life in locally advanced or metastatic renal cell carcinoma (mRCC). However, survival extension with this approach would be scarce and not exempt from adverse events, thus preventing its recommendation in an already frail patient. An evidence based analysis on the role of surgery in each of the possible clinical scenarios involved under this heading may provide a clear picture on this issue and would be of value in the decision making process...
January 25, 2018: Expert Review of Anticancer Therapy
Hideaki Miyake, Takayuki Sugiyama, Ryota Aki, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Atsushi Otsuka
BACKGROUND: To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy. METHODS: This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy. RESULTS: Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively...
January 13, 2018: International Journal of Clinical Oncology
Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Hidekazu Tachibana, Kazuhiko Yoshida, Kenji Omae, Junpei Iizuka, Hirohito Kobayashi, Kazunari Tanabe
BACKGROUND: The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. METHODS: The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy...
January 11, 2018: International Journal of Clinical Oncology
Hironori Fukuda, Toshio Takagi, Tsunenori Kondo, Kazuhiko Yoshida, Satoru Shimizu, Yoji Nagashima, Kazunari Tanabe
BACKGROUND: The aim of the present study was to evaluate the prognostic significance of the Glasgow Prognostic Score (GPS) in metastatic renal cell carcinoma (mRCC) patients treated by cytoreductive nephrectomy (CN), and the accuracy of the GPS as a prognostic factor. METHODS: We retrospectively analyzed the data of patients who underwent CN for mRCC between March 1984 and August 2015. In accordance with the GPS criteria, the patients were classified into three groups: GPS 0: C-reactive protein (CRP) ≤ 1...
January 5, 2018: International Journal of Clinical Oncology
Paulo G Bergerot, Cristiane D Bergerot, Nazli Dizman, Stenio Zequi, Andre Fay, Yash Dara, Manuel Caitano Maia, Brendan N Cotta, Edna Prado Gonçalves, Maria Nirvana Formiga, Milena Shizue Tariki, Diego Abreu Clavijo, Toni K Choueiri, Gilberto Lopes, Sumanta K Pal
Background Although multiple therapies have emerged for the treatment of metastatic renal cell carcinoma (mRCC), it is unclear whether application of these agents is consistent in developed and developing countries. We sought to determine patterns of care for mRCC in Brazil as a representative developing country. Material and Methods A commercial database was used to acquire information pertaining to patients with mRCC receiving treatment at private or public hospitals in Brazil between March 2013 and October 2016...
December 27, 2017: Journal of Global Oncology
Alexandr Poprach, Ondrej Fiala, Renata Chloupkova, Bohuslav Melichar, Radek Lakomy, Katarina Petrakova, Milada Zemanova, Katerina Kopeckova, Ondrej Slaby, Hana Studentova, Jindrich Kopecký, Igor Kiss, Jindrich Finek, Ladislav Dusek, Tomas Buchler
BACKGROUND: Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. PATIENTS AND METHODS: The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. RESULTS: Median progression-free and overall survival were 12...
January 2018: Anticancer Research
Tala Achkar, Ananth Arjunan, Hong Wang, Melissa Saul, Diwakar Davar, Leonard J Appleman, David Friedland, Rahul A Parikh
BACKGROUND: High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12-20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10-15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2...
2017: PloS One
Renate Pichler, Isabel Heidegger
The era of antiangiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway has become a mainstay in the treatment of metastatic renal cell carcinoma (mRCC), showing primary responses in 65-70% of patients. Nevertheless, most of those patients progress to angiogenesis inhibitors over time due to different modes of resistance (adaptive and intrinsic). Both in vitro and in vivo analyses provided evidence that PD-L1 upregulation in hypoxia conditions is dependent on hypoxia-inducible factor (HIF)-2alpha and is associated with an overexpression of VEGF...
2017: Memo
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