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Yuichi Arai, Keiichi Ito, Kazuyoshi Tachi, Akio Koga, Yusuke Shinchi, Ayako Masunaga, Makoto Isono, Tomohiko Asano
A 73-year-old male patient underwent a right nephrectomy for renal cell carcinoma in 2008, and interferon-alpha was initiated as adjuvant treatment. Computed tomography (CT) scans showed lymphadenopathy above the left diaphragm, and treatment with interferon-2 was subsequently initiated in 2009. Nasal bleeding manifested in February 2010, and CT scans showed a soft-tissue density mass mainly located in the ethmoid sinus. A biopsy of the lesion was performed, and metastatic renal cell carcinoma was diagnosed...
September 2016: Hinyokika Kiyo. Acta Urologica Japonica
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
Pardhasaradhi Mathi, Ganesh Kumar Veeramachaneni, K Kranthi Raj, Venkateswara Rao Talluri, Venkata Raman Bokka, Mahendran Botlagunta
Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract...
October 2016: Journal of Molecular Modeling
Fumi Kawakami, Priya Rao, Pheroze Tamboli, Christopher G Wood, Jose A Karam
PURPOSE: The aim of this study is to evaluate histological changes in tumor-parenchymal interface in clear cell renal cell carcinoma (ccRCC) after neoadjuvant axitinib treatment. PATIENTS AND METHODS: We obtained clinical and pathology materials from 23 ccRCC patients treated with neoadjuvant axitinib in a phase II clinical trial, and from 23 matched patients with ccRCC that had upfront surgery. Histology of the tumor pseudocapsule and peritumoral kidney parenchymal change was evaluated and compared between the 2 cohorts...
September 24, 2016: Journal of Urology
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
September 10, 2016: Cancer Treatment Reviews
Gregory S Alexander, Joshua D Palmer, Madalina Tuluc, Jianqing Lin, Adam P Dicker, Voichita Bar-Ad, Larry A Harshyne, Jennifer Louie, Colette M Shaw, D Craig Hooper, Bo Lu
BACKGROUND: Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment...
2016: Journal of Hematology & Oncology
Moshe C Ornstein, Laura Wood, Paul Elson, Kimberly Allman, Jennifer Beach, Allison Martin, Timothy Gilligan, Jorge A Garcia, Brian I Rini
BACKGROUND: Given the variability in drug levels with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC), dose escalation at the occurrence of progressive disease (PD) might have antitumor effects. PATIENTS AND METHODS: The data from patients with mRCC who were treated at the Cleveland Clinic with TKIs and received a dose escalation after PD in accordance with Response Evaluation Criteria In Solid Tumors (RECIST), version 1...
August 18, 2016: Clinical Genitourinary Cancer
Sebastiano Buti, Alessandro Leonetti, Alice Dallatomasina, Melissa Bersanelli
INTRODUCTION: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. AIM: The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. EVIDENCE REVIEW: Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI)...
2016: Core Evidence
M Soto, R Campanario, R Saiz, A Juárez
OBJECTIVSE: To describe the complete responses in our patients with metastatic renal cancer treated with tyrosine kinase inhibitors. MATERIAL AND METHODS: Between June 2007 and December 2014 we treated in our department 43 patients with metastatic renal cancer with antiangiogenic drugs. RESULTS: 9.3% (4/43) of the patients treated with antiangiogenic drugs obtained complete response according to RECIST 1.1 criteria. In 3 of the 4 patients, complete response was obtained during the first-line treatment with sunitinib at doses of 50 mgr/day in a 4/2 scheme and the remaining patient obtained it with second line axitinib at doses of 10 mgr/day...
September 2016: Archivos Españoles de Urología
Hiroshi Kato, Naoto Sassa, Masayuki Miyazaki, Mio Takeuchi, Miho Asai, Akane Iwai, Yukihiro Noda, Momokazu Gotoh, Kiyofumi Yamada
PURPOSE: Axitinib is a selective tyrosine kinase inhibitor of VEGF receptors, approved for advanced renal cell carcinoma (RCC). Associations between axitinib plasma exposure, genetic polymorphisms of ABC transporters and axitinib-induced toxicities have not been adequately explored. METHODS: Twenty RCC patients treated with axitinib were enrolled in this study. Blood samples were collected 0, 0.5, 1, 2, 4, and 6 h after administration of axitinib on day 1 and at steady state...
October 2016: Cancer Chemotherapy and Pharmacology
Yoshihiko Tomita, Satoshi Fukasawa, Mototsugu Oya, Hirotsugu Uemura, Nobuo Shinohara, Tomonori Habuchi, Brian I Rini, Ying Chen, Angel H Bair, Seiichiro Ozono, Seiji Naito, Hideyuki Akaza
OBJECTIVES: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. METHODS: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period...
August 29, 2016: Japanese Journal of Clinical Oncology
A L Ho, L Dunn, E J Sherman, M G Fury, S S Baxi, R Chandramohan, S Dogan, L G T Morris, G D Cullen, S Haque, C S Sima, A Ni, C R Antonescu, N Katabi, D G Pfister
BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Maria Serova, Annemilaï Tijeras-Raballand, Celia Dos Santos, Matthieu Martinet, Cindy Neuzillet, Alfred Lopez, Dianne C Mitchell, Brad A Bryan, Guillaume Gapihan, Anne Janin, Guilhem Bousquet, Maria Eugenia Riveiro, Ivan Bieche, Sandrine Faivre, Eric Raymond, Armand de Gramont
Angiogenesis is hallmark of clear cell renal cell carcinogenesis. Anti-angiogenic therapies have been successful in improving disease outcome; however, most patients treated with anti-angiogenic agents will eventually progress. In this study we report that clear cell renal cell carcinoma was associated with vasculogenic mimicry in both mice and human with tumor cells expressing endothelial markers in the vicinity of tumor vessels. We show that vasculogenic mimicry was efficiently targeted by sunitinib but eventually associated with tumor resistance and a more aggressive phenotype both in vitro and in vivo...
June 21, 2016: Oncotarget
Thomas E Hutson, Salman Al-Shukri, Viktor P Stus, Oleg N Lipatov, Yaroslav Shparyk, Angel H Bair, Brad Rosbrook, Glen I Andrews, Nicholas J Vogelzang
BACKGROUND: In a randomized phase III trial in treatment-naive patients with metastatic renal cell carcinoma (RCC), axitinib versus sorafenib yielded numerically longer progression-free survival (median, 10.1 vs. 6.5 months; hazard ratio [HR], 0.77; 1-sided P = .038) and significantly higher objective response rate (32% vs. 15%; 1-sided P = .0006). In this article, we report overall survival (OS) and updated safety results. PATIENTS AND METHODS: Previously untreated patients with metastatic RCC (n = 288), stratified according to Eastern Cooperative Oncology Group performance status (ECOG PS; 0 vs...
May 27, 2016: Clinical Genitourinary Cancer
Paul Slobbe, Alex J Poot, Rianne Haumann, Robert C Schuit, Albert D Windhorst, Guus A M S van Dongen
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([(11)C]erlotinib and [(18)F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers, [(11)C]axitinib and [(11)C]nintedanib, and to evaluate their potential for PET. METHODS: Following successful tracer synthesis, biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were performed...
October 2016: Nuclear Medicine and Biology
C Rothermundt, J von Rappard, T Eisen, B Escudier, V Grünwald, J Larkin, D McDermott, J Oldenburg, C Porta, B Rini, M Schmidinger, C N Sternberg, P M Putora
BACKGROUND: Second-line systemic treatment options for metastatic clear cell renal cell cancer (mccRCC) are diverse and treatment strategies are variable among experts. Our aim was to investigate the approach for the second-line treatment after first-line therapy with a tyrosine kinase inhibitor (TKI). Recently two phase III trials have demonstrated a potential role for nivolumab (NIV) and cabozantinib (CAB) in this setting. We aimed to estimate the impact of these trials on clinical decision making...
August 3, 2016: World Journal of Urology
Hideaki Miyake, Ken-Ichi Harada, Seiichiro Ozono, Masato Fujisawa
PURPOSE: To comprehensively analyze the efficacy of axitinib for metastatic renal-cell carcinoma (mRCC) patients. PATIENTS AND METHODS: This study included 124 consecutive Japanese patients treated with axitinib as second-line systemic therapy for mRCC in a routine clinical setting. RESULTS: In addition to 4 indeterminate patients (3.2%), 0 (0%), 21 (16.9%), 87 (70.2%), and 12 (9.7%) were judged to show complete response, partial response, stable disease, and progressive disease, respectively, as the best responses to axitinib...
July 5, 2016: Clinical Genitourinary Cancer
Laurent Claret, Jenny Zheng, Francois Mercier, Pascal Chanu, Ying Chen, Brad Rosbrook, Pithavala Yazdi, Peter A Milligan, Rene Bruno
PURPOSE: To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. METHODS: Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models...
September 2016: Cancer Chemotherapy and Pharmacology
Hideaki Miyake, Ken-Ichi Harada, Seiichiro Ozono, Masato Fujisawa
The objective of this study was to analyze the impact of age on clinical outcomes of metastatic renal cell carcinoma (mRCC) patients receiving axitinib. This study included 144 consecutive mRCC patients who received axitinib for at least 12 weeks as second-line therapy in a routine clinical setting. The efficacy, safety and quality of life (QOL) were compared between patients aged <75 (n = 116) and ≥75 (n = 28) years. No significant differences in the clinicopathological characteristics were noted between younger and older patients...
August 2016: Medical Oncology
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