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https://www.readbyqxmd.com/read/28919822/uterine-sarcoma-current-perspectives
#1
REVIEW
Charlotte Benson, Aisha B Miah
Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28911730/management-of-tyrosine-kinase-inhibitors-tki-side-effects-in-differentiated-and-medullary-thyroid-cancer-patients
#2
REVIEW
C Resteghini, S Cavalieri, D Galbiati, R Granata, S Alfieri, C Bergamini, P Bossi, L Licitra, L D Locati
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28903416/overriding-tki-resistance-of-renal-cell-carcinoma-by-combination-therapy-with-il-6-receptor-blockade
#3
Kei Ishibashi, Tobias Haber, Ines Breuksch, Susanne Gebhard, Takashi Sugino, Hitoshi Kubo, Junya Hata, Tomoyuki Koguchi, Michihiro Yabe, Masao Kataoka, Soichiro Ogawa, Hiroyuki Hiraki, Tomohiko Yanagida, Nobuhiro Haga, Joachim W Thüroff, Dirk Prawitt, Walburgis Brenner, Yoshiyuki Kojima
Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902533/randomized-phase-iii-trial-of-adjuvant-pazopanib-versus-placebo-after-nephrectomy-in-patients-with-localized-or-locally-advanced-renal-cell-carcinoma
#4
Robert J Motzer, Naomi B Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae Lyun Lee, Bohuslav Melichar, Brian I Rini, Toni K Choueiri, Milada Zemanova, Lori A Wood, M Neil Reaume, Arnulf Stenzl, Simon Chowdhury, Ho Yeong Lim, Ray McDermott, Agnieszka Michael, Weichao Bao, Marlene J Carrasco-Alfonso, Paola Aimone, Maurizio Voi, Christian Doehn, Paul Russo, Cora N Sternberg
Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135)...
September 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28891933/tyrosine-kinase-inhibitors-therapies-with-mainly-anti-angiogenic-activity-in-advanced-renal-cell-carcinoma-value-of-pet-ct-in-response-evaluation
#5
REVIEW
Girolamo Ranieri, Ilaria Marech, Artor Niccoli Asabella, Alessandra Di Palo, Mariangela Porcelli, Valentina Lavelli, Giuseppe Rubini, Cristina Ferrari, Cosmo Damiano Gadaleta
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28869476/pazopanib-reduces-phosphorylated-tau-levels-and-alters-astrocytes-in-a-mouse-model-of-tauopathy
#6
Monica Javidnia, Michaeline L Hebron, Yue Xin, Nikolas G Kinney, Charbel E-H Moussa
Hyperphosphorylation and aggregation of tau protein is a critical factor in many neurodegenerative diseases. These diseases are increasing in prevalence, and there are currently no cures. Previous work from our group and others has shown that tyrosine kinase inhibitors (TKIs) can stimulate autophagy, decrease pathological proteins, and improve symptoms in models of neurodegeneration. Here we examined the role of pazopanib in mouse models that express either human mutant P301L tau (TauP301L) or triple mutant amyloid precursor protein (3x-AβPP)...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28860410/next-generation-sequencing-for-patients-with-sarcoma-a-single-center-experience
#7
Gregory M Cote, Jie He, Edwin Choy
BACKGROUND: Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next-generation sequencing (NGS) platform in clinic patients. MATERIALS AND METHODS: We retrospectively analyzed results of NGS using 133 tumor samples from patients diagnosed with a variety of sarcomas that were analyzed with targeted NGS covering over 400 cancer-related genes (405 DNA, 265 RNA) on a commercially available platform...
August 31, 2017: Oncologist
https://www.readbyqxmd.com/read/28856074/utilizing-tumor-and-plasma-liquid-biopsy-in-treatment-decision-making-for-an-estrogen-receptor-positive-advanced-breast-cancer-patient
#8
Bing Xu, Amy Krie, Pradip De, Casey Williams, Rachel Elsey, Jessica Klein, Brian Leyland-Jones
Breast cancer affects 12% of females in the United States and is the leading cause of cancer death in the female population. Personalized therapy is being used in clinical practice to treat breast cancer based on tumor molecular profiling, which can be obtained from tissue biopsy or plasma liquid biopsy as circulating tumor deoxyribonucleic acid (ctDNA). The available ctDNA tests provide a non-invasive way to monitor the cancer genome in a real-time manner. In this case report, a 38-year-old female with recurrent estrogen receptor (ER) positive breast cancer is treated with letrozole, everolimus, and palbociclib...
June 29, 2017: Curēus
https://www.readbyqxmd.com/read/28844815/pazopanib-for-advanced-liposarcoma
#9
Judith A Gilbert
No abstract text is available yet for this article.
August 24, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28842319/quantitative-phosphoproteomic-analysis-of-acquired-cancer-drug-resistance-to-pazopanib-and-dasatinib
#10
Simon Vyse, Frank McCarthy, Malgorzata Broncel, Angela Paul, Jocelyn P Wong, Amandeep Bhamra, Paul H Huang
Acquired drug resistance impacts the majority of patients being treated with tyrosine kinase inhibitors (TKIs) and remains a key challenge in modern anti-cancer therapy. The lack of clinically effective therapies to overcome resistance represents an unmet need. Understanding the signalling that drives drug resistance will facilitate the development of new salvage therapies to treat patients with secondary TKI resistance. In this study, we utilise mass spectrometry to characterise the global phosphoproteomic alterations that accompany the acquisition of resistance to two FDA-approved TKIs, pazopanib and dasatinib, in the A204 rhabdoid tumour cell line...
August 22, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28835514/salvage-therapy-in-advanced-adult-soft-tissue-sarcoma-a-systematic-review-and-meta-analysis-of-randomized-trials
#11
REVIEW
Alessandro Comandone, Fausto Petrelli, Antonella Boglione, Sandro Barni
BACKGROUND: Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded. MATERIAL AND METHODS: PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS...
August 23, 2017: Oncologist
https://www.readbyqxmd.com/read/28832986/results-of-a-prospective-phase-2-study-of-pazopanib-in-patients-with-advanced-intermediate-grade-or-high-grade-liposarcoma
#12
Brian L Samuels, Sant P Chawla, Neeta Somaiah, Arthur P Staddon, Keith M Skubitz, Mohammed M Milhem, Pamela E Kaiser, David C Portnoy, Dennis A Priebat, Mark S Walker, Edward J Stepanski
BACKGROUND: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma. METHODS: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor...
August 18, 2017: Cancer
https://www.readbyqxmd.com/read/28823141/targeted-therapy-of-ovarian-cancer-including-immune-check-point-inhibitor
#13
REVIEW
Jin Young Kim, Chi Heum Cho, Hong Suk Song
Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects...
September 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#14
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#15
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28801802/does-dose-modification-affect-efficacy-of-first-line-pazopanib-in-metastatic-renal-cell-carcinoma
#16
Paolo Grassi, Elena Verzoni, Raffaele Ratta, Luca Porcu, Michele Prisciandaro, Alessia Mennitto, Giuseppina Calareso, Filippo de Braud, Giuseppe Procopio
BACKGROUND: Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear. OBJECTIVES: Our objective was to conduct a retrospective analysis to investigate the clinical effect of different therapeutic doses of first-line pazopanib in patients with mRCC...
August 11, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28800271/overall-survival-in-the-randomized-phase-ii-study-investigating-pazopanib-versus-weekly-paclitaxel-in-relapsed-or-progressive-urothelial-cancer
#17
Miki Horiguchi, Hajime Uno, Lee-Jen Wei
No abstract text is available yet for this article.
August 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28761748/new-treatment-options-for-metastatic-renal-cell-carcinoma
#18
REVIEW
Alejo Rodriguez-Vida, Thomas E Hutson, Joaquim Bellmunt, Michiel H Strijbos
During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care...
2017: ESMO Open
https://www.readbyqxmd.com/read/28756707/emerging-vascular-endothelial-growth-factor-antagonists-to-treat-neovascular-age-related-macular-degeneration
#19
Rehan M Hussain, Thomas A Ciulla
Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability)...
August 4, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28754721/activity-of-pazopanib-and-trabectedin-in-advanced-alveolar-soft-part-sarcoma
#20
Silvia Stacchiotti, Olivier Mir, Axel Le Cesne, Bruno Vincenzi, Alexander Fedenko, Robert G Maki, Neeta Somaiah, Shreyaskumar Patel, Mehedi Brahmi, Jean Y Blay, Kjetil Boye, Kirsten Sundby Hall, Hans Gelderblom, Nadia Hindi, Javier Martin-Broto, Hanna Kosela, Piotr Rutkowski, Antoine Italiano, Florence Duffaud, Eisuke Kobayashi, Paolo G Casali, Salvatore Provenzano, Akira Kawai
BACKGROUND: Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second-line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi-institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin...
July 28, 2017: Oncologist
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