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https://www.readbyqxmd.com/read/28439491/translating-new-data-to-the-daily-practice-in-second-line-treatment-of-renal-cell-carcinoma-the-role-of-tumor-growth-rate
#1
EDITORIAL
Enrique Grande, Olga Martínez-Sáez, Pablo Gajate-Borau, Teresa Alonso-Gordoa
The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28426267/a-phase-2-trial-of-single-agent-axitinib-as-maintenance-therapy-following-first-line-treatment-with-modified-folfox-bevacizumab-in-patients-with-metastatic-colorectal-cancer
#2
Johanna C Bendell, Mathew Joseph, Kirk Barnes, Mark Mainwaring, Dianna Shipley, Chandra Reddy, Laura Blakely, Ronald Blachly, Cassie M Lane, Chris Earwood, Michel Kuzur
This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for patients with metastatic colorectal cancer (mCRC) following first-line treatment with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed by axitinib maintenance after four cycles. The primary endpoint was progression-free survival (PFS). Seventy patients were enrolled. Common treatment-related toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral neuropathy during axitinib treatment...
April 20, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#3
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#4
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28388255/boosting-axitinib-exposure-with-a-cyp3a4-inhibitor-making-axitinib-treatment-personal
#5
Floor J E Lubberman, Nielka P van Erp, Rob Ter Heine, Carla M L van Herpen
No abstract text is available yet for this article.
April 7, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28378918/a-pharmacometric-framework-for-axitinib-exposure-efficacy-and-safety-in-metastatic-renal-cell-carcinoma-patients
#6
Emilie Schindler, Michael A Amantea, Mats O Karlsson, Lena E Friberg
The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, 2, 3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP) and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker time-courses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, 2 and 3 production, and VEGF degradation...
April 5, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28369747/bioengineered-three-dimensional-co-culture-of-cancer-cells-and-endothelial-cells-a-model-system-for-dual-analysis-of-tumor-growth-and-angiogenesis
#7
Geraldine Giap Ying Chiew, Na Wei, Samiksha Sultania, Sierin Lim, Kathy Qian Luo
Angiogenesis marks the transformation of a benign local tumor into a life-threatening disease. Many in vitro assays are available on two-dimensional (2D) platforms, however, limited research has been conducted to investigate the behavior of tumors and endothelial cells (ECs) grown on three-dimensional (3D) platforms. This study provides a 3D co-culture spheroid of tumor cells with endothelial cells (ECs) to study the interplay between ECs and tumor cells. In a 3D co-culture with HepG2 hepatocellular carcinoma (HCC) cells, ECs differentiate to form tubule networks when in co-culture...
March 28, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28361451/long-term-duration-of-first-line-axitinib-treatment-in-advanced-renal-cell-carcinoma
#8
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/28333125/clarity-reveals-dynamics-of-ovarian-follicular-architecture-and-vasculature-in-three-dimensions
#9
Yi Feng, Peng Cui, Xiaowei Lu, Brian Hsueh, Fredrik Möller Billig, Livia Zarnescu Yanez, Raju Tomer, Derek Boerboom, Peter Carmeliet, Karl Deisseroth, Aaron J W Hsueh
Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#10
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#11
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#12
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28267243/overall-survival-of-1st-line-axitinib-in-metastatic-renal-cell-carcinoma-japanese-subgroup-analysis-from-phase-ii-study
#13
Mototsugu Oya, Yoshihiko Tomita, Satoshi Fukasawa, Nobuo Shinohara, Tomonori Habuchi, Brian I Rini, Yosuke Fujii, Yoichi Kamei, Yoshiko Umeyama, Angel H Bair, Hirotsugu Uemura
Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and updated safety in 44 Japanese patients and compared with 169 non-Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first-line metastatic RCC were explored using a Cox proportional hazard model in all patients...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28256961/gemcitabine-mono-therapy-versus-gemcitabine-plus-targeted-therapy-in-advanced-pancreatic-cancer-a-meta-analysis-of-randomized-phase-iii-trials
#14
REVIEW
Alessandro Ottaiano, Monica Capozzi, Chiara De Divitiis, Alfonso De Stefano, Gerardo Botti, Antonio Avallone, Salvatore Tafuto
BACKGROUND: Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine. METHODS: Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected...
March 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28253548/patterns-of-care-among-patients-receiving-sequential-targeted-therapies-for-advanced-renal-cell-carcinoma-a-retrospective-chart-review-in-the-usa
#15
Sumanta K Pal, James E Signorovitch, Nanxin Li, Miriam L Zichlin, Zhimei Liu, Sameer R Ghate, Jose Ricardo Perez, Nicholas J Vogelzang
OBJECTIVES: To assess real-world treatment patterns of targeted therapies after failure of first-line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma. METHODS: A large, retrospective review of medical charts of patients with advanced renal cell carcinoma in the USA was carried out. Descriptive statistics were used to summarize physicians' and patients' characteristics, treatment sequences, and reasons for treatment choices. P-values were calculated using χ(2) -tests for categorical variables and Wilcoxon rank-sum tests for continuous variables...
April 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28246756/-first-line-therapy-in-advanced-renal-cell-carcinoma-a-randomized-open-label-phase%C3%A2-iii-study-evaluating-the-efficacy-and-safety-of-pembrolizumab-mk-3475-in-combination-with-axitinib-compared-to-sunitinib-monotherapy-as-first-line-treatment-for-locally-advanced
#16
https://www.readbyqxmd.com/read/28245539/-a-case-of-hydrocephalus-due-to-brain-metastasis-from-renal-cell-carcinoma-successfully-treated-with-axitinib
#17
Soichiro Shimura, Dai Koguchi, Satoru Minamida, Yoshinori Taoka, Masatsugu Iwamura
We report a case of hydrocephalus due to brain metastasis from renal cell carcinoma treated with axitinib. A 65-year-old man had undergone right radical nephrectomy for renal cell carcinoma in 2010. The pathological diagnosis indicated clear cell carcinoma G3, pT1a. After adjuvant treatment with interferon-α, computed tomography, in 2011, revealed multiple lung metastases. He was administered sorafenib. Because of progressive lung metastases, sunitinib was administered. The lung metastases were progressive and bone scan revealed multiple bone metastases...
January 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28230776/effects-and-side-effects-of-using-sorafenib-and-sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#18
REVIEW
Caroline Randrup Hansen, Daniela Grimm, Johann Bauer, Markus Wehland, Nils E Magnusson
In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28222071/combination-of-the-histone-deacetylase-inhibitor-vorinostat-with-bevacizumab-in-patients-with-clear-cell-renal-cell-carcinoma-a-multicentre-single-arm-phase-i-ii-clinical-trial
#19
Roberto Pili, Glenn Liu, Sreenivasulu Chintala, Hendrick Verheul, Shabnam Rehman, Kristopher Attwood, Martin A Lodge, Richard Wahl, James I Martin, Kiersten Marie Miles, Silvia Paesante, Remi Adelaiye, Alejandro Godoy, Serina King, James Zwiebel, Michael A Carducci
BACKGROUND: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28174388/-a-case-of-renal-cell-carcinoma-with-high-everolimus-blood-concentrations-and-hyperglycemia-due-to-everolimus-induced-hepatic-dysfunction
#20
Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
We report the case of a patient who had renal cell carcinoma with high everolimus blood concentrations and hyperglycemia due to everolimus-induced hepatic dysfunction. A 74-year-old man who underwent right nephrectomy for renal cell carcinoma was administered everolimus for multiple lung metastases. Everolimus caused grade 3 hepatic dysfunction and hyperglycemia; hence, high blood levels of everolimus were observed. Although the patient was re-administrated everolimus after recovering from hepatic dysfunction, hepatic function test values worsened again...
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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