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https://www.readbyqxmd.com/read/28209496/uterine-leiomyosarcoma-epidemiology-contemporary-treatment-strategies-and-the-impact-of-uterine-morcellation
#1
Stephanie Ricci, Rebecca L Stone, Amanda N Fader
Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma...
February 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28208511/re-first-line-sunitinib-versus-pazopanib-in-metastatic-renal-cell-carcinoma-results-from-the-international-metastatic-renal-cell-carcinoma-database-consortium
#2
https://www.readbyqxmd.com/read/28197036/induction-of-trismus-by-sunitinib-and-pazopanib-in-metastatic-renal-cell-carcinoma
#3
Ridhima Iyer, Bruce Montgomery, Hardev S Pandha
Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.
January 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28185218/clinical-pharmacokinetics-and-pharmacodynamics-of-pazopanib-towards-optimized-dosing
#4
REVIEW
Remy B Verheijen, Jos H Beijnen, Jan H M Schellens, Alwin D R Huitema, Neeltje Steeghs
Pazopanib is an inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor and stem cell receptor c-Kit, and has been approved for the treatment of renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib are complex and are characterized by pH-dependent solubility, large interpatient variability and low, non-linear and time-dependent bioavailability. Exposure to pazopanib is increased by both food and coadministration of ketoconazole, but drastically reduced by proton pump inhibitors...
February 10, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28176365/high-efficacy-of-pazopanib-on-an-undifferentiated-spindle-cell-sarcoma-resistant-to-first-line-therapy-is-identified-with-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#5
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Arun S Singh, Scott D Nelson, Sarah Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant cancer. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). In the present study, we evaluated the efficacy of standard first-line chemistry of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model. A high-grade USCS from a striated muscle of the patients was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model...
February 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28173774/treatment-patterns-and-survival-in-an-exhaustive-french-cohort-of-pazopanib-eligible-patients-with-metastatic-soft-tissue-sarcoma-sts
#6
Isabelle Ray-Coquard, Olivier Collard, Françoise Ducimetiere, Mathieu Laramas, Florence Mercier, Nadine Ladarre, Stephanie Manson, Bertrand Tehard, Sébastien Clippe, Jean-Philippe Suchaud, Laetitia Stefani, Jean-Yves Blay
BACKGROUND: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07. METHODS: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed. RESULTS: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28156651/oams-at-the-end-the-end-of-the-beginning-or-the-beginning-of-the-end
#7
Barbara Marie Galligan, Chintan Shah, Iris Chen Zhao, Brian Paciotti, Nathan Fairman, Quy Tran
: 229 Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152737/financial-risk-sharing-agreements-using-options-to-make-marginal-benefits-cost-effective
#8
(no author information available yet)
: 41 Background: New cancer treatments have become increasingly costly. Although new drugs may be sufficiently cost-efficiency for a primary indication (i1) to receive funding, subsequent indications (ia) may not prove cost-effective. A financial risk-sharing agreement to increase access is proposed. A potential 2012 real-world implementation in Canada for pazopanib use in metastatic renal cell carcinoma (mRCC) as i1, and soft-tissue sarcoma (STS) as ia is presented. METHODS: The market value of an indication can be approximated by its net-present-value (NPV) of expected cash flows...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152689/comparative-effectiveness-research-in-renal-cell-carcinoma-lenvatinib-with-everolimus-as-a-potential-new-treatment-option
#9
Corey Pelletier, Unnati Majethia, Anna Forsythe
: 27 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer and represents about 90% of all kidney cancers. As comprehensive comparison of the efficacy associated with mRCC treatments is not available, the goal of this research was to provide a comparative effectiveness analysis including overall survival (OS) and progression free survival (PFS) for first and second line treatments. METHODS: Systematic literature review yielded the following randomized active-controlled studies: lenvatinib + everolimus (LEN+EVE) versus everolimus (EVE), axinitib (AXI) versus sorafenib (SOR), cabozantinib (CAB) versus EVE, nivolumab (NIV) versus EVE, and pazopanib (PAZ) versus sunitinib (SUN)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#10
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28144093/managing-metastatic-renal-cell-carcinoma-challenges-pitfalls-and-outcomes-in-the-real-world
#11
Karnam Ashok Kumar, Gundeti Sadashivudu, K V Krishnamani, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
INTRODUCTION: Renal cell carcinoma (RCC) is the most common cancer of the kidney accounting for 85% of renal tumors. Metastatic RCC (mRCC) had a poor prognosis and with the introduction of tyrosine-kinase inhibitors, such as sunitinib, pazopanib the outcomes improved. There is only one study reported from India on the use of sunitinib in mRCC. We present our analysis of mRCC and use of sunitinib at our institute over 5 years. MATERIALS AND METHODS: All patients with mRCC receiving sunitinib were analyzed with respect to patient characteristics, response, toxicity, and outcomes...
October 2016: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28143997/targeted-therapy-for-metastatic-renal-cell-carcinoma
#12
REVIEW
Andika Afriansyah, Agus Rizal Ah Hamid, Chaidir A Mochtar, Rainy Umbas
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC...
October 2016: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28139444/real-world-survival-outcomes-and-prognostic-factors-among-patients-receiving-first-targeted-therapy-for-advanced-renal-cell-carcinoma-a-seer-medicare-database-analysis
#13
Sumanta K Pal, Sameer R Ghate, Nanxin Li, Elyse Swallow, Miranda Peeples, Miriam L Zichlin, Jose Ricardo Perez, Neeraj Agarwal, Nicholas J Vogelzang
BACKGROUND: The real-world survival outcomes and prognostic factors among patients receiving first-line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. PATIENTS AND METHODS: Adult patients diagnosed with RCC and treated with first-line targeted therapy were identified from the Surveillance, Epidemiology, and End Results-Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006-2009) or late (2010-2012) targeted therapy era cohorts by the year of the first-line targeted therapy initiation...
January 5, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28120901/patient-specific-hepatocyte-like-cells-derived-from-induced-pluripotent-stem-cells-model-pazopanib-mediated-hepatotoxicity
#14
Yukti Choudhury, Yi Chin Toh, Jiangwa Xing, Yinghua Qu, Jonathan Poh, Li Huan, Hui Shan Tan, Ravindran Kanesvaran, Hanry Yu, Min-Han Tan
Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108284/first-line-pazopanib-in-non-clear-cell-renal-carcinoma-the-italian-retrospective-multicenter-panorama-study
#15
Sebastiano Buti, Melissa Bersanelli, Francesca Maines, Gaetano Facchini, Francesco Gelsomino, Fable Zustovich, Matteo Santoni, Elena Verri, Ugo De Giorgi, Cristina Masini, Franco Morelli, Maria Giuseppa Vitale, Teodoro Sava, Giuseppe Prati, Carmelinda Librici, Anna Paola Fraccon, Giuseppe Fornarini, Marco Maruzzo, Francesco Leonardi, Orazio Caffo
INTRODUCTION: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients. PATIENTS AND METHODS: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed...
December 29, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28103739/newer-medical-therapies-for-metastatic-soft-tissue-sarcoma
#16
Akash Tiwari, Vineet Govinda Gupta, Sameer Bakhshi
Metastatic/advanced soft tissue sarcoma has a poor prognosis conventionally, treatment options have been limited. In recent years, this area has been a rich ground for research with many new drugs being approved and several more in the pipeline. With multiple new treatment options available, it is vital to keep up pace with this rapidly changing field. Areas covered: Recent data regarding use of novel agents in advanced soft tissue sarcoma is reviewed with a focus on clinical applicability. The goal is to guide the clinician into choosing appropriate lines of therapy for the individual patient in light of recent availability of multiple new treatment options...
February 6, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28099210/pazopanib-a-promising-option-for-the-treatment-of-aggressive-fibromatosis
#17
Zoltan Szucs, Christina Messiou, Han Hsi Wong, Helen Hatcher, Aisha Miah, Shane Zaidi, Winette T A van der Graaf, Ian Judson, Robin L Jones, Charlotte Benson
Desmoid tumour/aggressive fibromatosis (DT/AF) is a rare soft-tissue neoplasm that is locally aggressive but does not metastasize. There is no standard systemic treatment for symptomatic patients, although a number of agents are used. Tyrosine kinase inhibitors have recently been reported to show useful activity. We reviewed our bi-institutional (Royal Marsden Hospital, Cambridge University Hospitals) experience with the tyrosine kinase inhibitor pazopanib in the treatment of progressing DT/AF. Eight patients with DT/AF were treated with pazopanib at Royal Marsden Hospital and Cambridge University Hospitals between June 2012 and June 2016...
January 17, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#18
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28096934/first-line-treatment-options-in-metastatic-renal-cell-cancer
#19
REVIEW
Anil Kapoor
The introduction of targeted therapy a decade ago revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Currently recommended first-line treatments in Canada include sunitinib, pazopanib, and temsirolimus. With the heterogeneity of mRCC disease, the choice of treatment is driven largely by prognostic factors...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28089721/angiotensin-inhibitors-as-treatment-of-sunitinib-pazopanib-induced-hypertension-in%C3%A2-metastatic-renal-cell-carcinoma
#20
Patrick Penttilä, Juhana Rautiola, Tuija Poussa, Katriina Peltola, Petri Bono
BACKGROUND: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center...
December 22, 2016: Clinical Genitourinary Cancer
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