DOCSLIB.ORG

Tivozanib for Advanced Renal Cell Carcinoma – First Line January 2011

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tivozanib for Advanced Renal Cell Carcinoma – First Line January 2011 Tivozanib for advanced renal cell carcinoma – first line January 2011 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research January 2011 Tivozanib for advanced renal cell carcinoma – first line Target group • Renal cell carcinoma (RCC): advanced – first line. Technology description Tivozanib (AV-951; KRN-951) is a selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, which are involved in angiogenesis. Inhibition of VEGF driven angiogenesis has been demonstrated to reduce vascularisation of tumours, thereby suppressing tumour growth. Tivozanib is intended to substitute current therapies for the first line treatment of patients with advanced RCC. It is administered orally at 1.5mg once daily for 3 weeks in a 4 week cycle. Tivozanib is in phase I/II clinical trials for the treatment of breast cancer, gastrointestinal cancer and non-small cell lung cancer. Innovation and/or advantages If licensed, tivozanib will offer an additional first line treatment option for advanced RCC, a condition where current therapies offer relatively limited benefit. Developer AVEO Pharma Limited. Availability, launch or marketing dates, and licensing plans In phase III clinical trials. NHS or Government priority area This topic is relevant to the NHS Cancer Plan (2000) and Cancer Reform Strategy (2007). Relevant guidance • NICE technology appraisal in development. Pazopanib for the first line treatment of metastatic renal cell carcinoma. Expected May 20111. • NICE technology appraisal in development. Everolimus for the treatment of advanced and/or metastatic renal cell carcinoma. Expected date of issue to be confirmed2. • NICE technology appraisal in development. Pazopanib for the second line treatment of metastatic renal cell carcinoma. Suspended April 20103. • NICE technology appraisal. Bevacizumab (first-line), sorafenib (first- and second- line), sunitinib (second-line) and temsirolimus (first-line) for the treatment of advanced and/or metastatic renal cell carcinoma. 20094. • NICE technology appraisal. Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma. 20095. • NICE guidance on cancer services. Improving outcomes in urological cancers – the manual. 20026. 7 • European Association of Urology. Guidelines on renal cell carcinoma. 2010 . • Cancer Care Ontario - program in evidence-based care. Clinical practice guideline. The use of inhibitors of angiogenesis in patients with inoperable locally advanced or metastatic renal cell cancer: guideline recommendations. 20098. • Cancer Care Ontario - program in evidence-based care. Clinical practice guideline. Interferon-alfa in the treatment of patients with inoperable locally advanced or metastatic renal cell cancer: guideline recommendations. 20099. 2 January 2011 • National Comprehensive Cancer Network. Clinical practice guidelines in oncology: kidney cancer. 200810. • Peer Review Team - National Cancer Action Team. Revised urology cancer measures. 200811. • Cancer Care Ontario - program in evidence-based care. Clinical practice guideline. Interleukin-2 in the treatment of patients with unresectable or metastatic renal cell cancer. 200612. Clinical need and burden of disease RCC is the most common form of kidney cancer and accounts for around 3% of all adult cancers in the UK4. In England there were 16,306 admissions for kidney cancer (ICD C64-66, C68), resulting in 82,610 bed days and 19,241 finished consultant episodes in 2009-1013. In England and Wales, an estimated 90% of kidney cancers are RCCs14. Approximately 70-80% of all RCCs have a clear cell component15. RCC is nearly twice as common in men as in women, and most commonly affects adults aged 50-80 years4,16. In Europe, approximately 25% of cases of kidney cancer are attributable to obesity and 25% of cases in men are attributable to smoking7. Approximately 25% and 17% of patients present with advanced and/or metastatic disease (stage III or stage IV) respectively4, representing around 2,500 new patients per year17. In addition, an estimated 50% of patients who have curative resection for earlier stages will develop recurrent and/or metastatic disease4. The estimated five-year survival rate for RCC is 44%, which is reduced to 10% for metastatic disease4. In 2009, there were 3,317 deaths registered from kidney cancer (ICD C64-66, C68) in England and Wales18. Existing comparators and treatments Treatment of RCC is primarily surgical. The main objectives of medical intervention are to relieve physical symptoms and extend survival. Advanced and/or metastatic RCC is largely resistant to chemotherapy, radiotherapy and hormonal therapy. Until recently, the standard treatment was immunotherapy with interferon alpha (IFN-alpha), or less commonly interleukin-2 (IL-2)5. Not all patients are suitable for immunotherapy, which achieves overall response rates of 4-31%19, and is often associated with severe morbidity (physical and psychological side effects). In 2009, sunitinib (Sutent), a tyrosine kinase inhibitor, was recommended by NICE as a first line treatment for patients with advanced and/or metastatic RCC in whom immunotherapy would be suitable and who have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (typically mobile and can do light housework or office work)5. Pazopanib (Votrient) has recently received a positive NICE final appraisal determination (FAD) for the first line treatment of patients with advanced RCC who have not received prior cytokine therapy and have a ECOG performance status of 0-120. Other therapeutic options for the treatment of advanced or metastatic RCC that are licensed but not recommended by NICE include4,21,22: • Sunitinib (Sutent): second line therapy. • Sorafenib (Nexavar): first line therapy for patients unsuitable for cytokine therapy or second line therapy following cytokine failure. • Temsirolimus (Torisel): first line therapy in patients with >3 poor prognostic indicators. • Bevacizumab (Avastin): first line therapy in combination with IFN-alpha. • Everolimus (Afinitor): second line therapy after failure of VEGF targeted therapy. 3 January 2011 Efficacy and safety Trial TIVO-1, NCT01030783; NCT01076010; tivozanib NCT00502307; tivozanib or tivozanib or sorafenib; or sorafenib; phase III placebo; phase II. phase III. extension. Sponsor AVEO pharmaceuticals. AVEO pharmaceuticals. AVEO pharmaceuticals. Status Ongoing. Ongoing. Completed. Source of Trial registry23, Trial registry24, Abstract25,26, trial registry27, information manufacturer. manufacturer. manufacturer. Location EU (inc UK), USA, EU (inc UK), USA, India, Russia and Ukraine. Canada and other Canada and other countries. countries. Design Randomised, active- Extension study. Randomised, placebo- controlled. controlled. Participants n=500 (planned); adults; n=500 (planned); adults; n=272; adults; RCC; and schedule RCC; recurrent or RCC; recurrent or recurrent, metastatic or metastatic; CC component; metastatic; CC component; primary RCC not amendable undergone prior ECOG performance status to surgical intervention; nephrectomy; measurable 0-2; participated in trial measurable disease; received 0 disease as per RECISTa; NCT01030783; -1 prior systemic therapies; no received 0 -1 prior demonstrated disease prior treatment with VEGF- systemic therapiesb; no progression with sorafenib directed therapy; no active prior treatment with or clinical benefit and brain metastases; Karnofsky VEGF-directed therapy or acceptable tolerability with performance status ≥70%; life drug targeting mTORc tivozanib or sorafenib for expectancy ≥3 months. pathway; ECOG up to 2 years. Received tivozanib at 1.5mg performance status 0-1; Continued on the same once daily for 3 weeks in a 4 life expectancy ≥3 months; treatment as randomised in week cycle for 16 weeks. no active brain metastases. NCT01030783. Further treatment based on Randomised to tivozanib Participants who failed on tumour response. If <25% at 1.5mg once daily for 3 sorafenib in tumour change (growth or weeks of a 4 week cycle or NCT01030783 or during shrinkage) randomised to sorafenib at 400mg twice the extension study tivozanib at 1.5mg once daily daily in a 4 week cycle. crossed over to tivozanib. for 3 weeks of a 4 week cycle or placebo for 12 weeks; if ≥25% tumour shrinkage continued on tivozanib; and if ≥25% tumour growth discontinued treatment with tivozanib. Patients receiving placebo given the option to receive tivozanib after 12 weeks. Follow-up Patients with documented Active treatment until Active treatment period 12 stable disease or objective disease progression and/or weeks. Thereafter patients response receive treatment intolerable toxicities; with documented stable for up to 2 years. follow up until death. disease or objective response Thereafter they may enrol receive treatment until disease in a separate long-term progression and/or treatment protocol. unacceptable toxicities. Treatment continues until disease progression and/or unacceptable toxicities. aResponse Evaluation Criteria In Solid Tumors. bImmunotherapy including INF-alfa or IL-2 based therapy, chemotherapy, hormonal therapy or an investigational agent. cMammalian target of rapamycin. 4 January 2011 Follow up
Load more

Recommended publications
  • Novel Drug Candidates for Blast Phase Chronic Myeloid Leukemia from High-Throughput Drug Sensitivity and Resistance Testing
    OPEN Citation: Blood Cancer Journal (2015) 5, e309; doi:10.1038/bcj.2015.30 www.nature.com/bcj ORIGINAL ARTICLE Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing PO Pietarinen1, T Pemovska2, M Kontro1, B Yadav2, JP Mpindi2, EI Andersson1, MM Majumder2, H Kuusanmäki2, P Koskenvesa1, O Kallioniemi2, K Wennerberg2, CA Heckman2, S Mustjoki1,3 and K Porkka1,3 Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.
    [Show full text]
  • A Systematic Review and Meta-Analysis Comparing The
    EUROPEAN UROLOGY 71 (2017) 426–436 available at www.sciencedirect.com journal homepage: www.europeanurology.com Review – Kidney Cancer A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear[3_TD$IF] Cell Renal Cell Carcinoma Sergio Ferna´ndez-Pello a,[3_TD$IF] Fabian Hofmann b, Rana Tahbaz c, Lorenzo Marconi d, Thomas B. Lam e,f, Laurence Albiges g, Karim Bensalah h, Steven E. Canfield i, Saeed Dabestani j, Rachel H. Giles k, Milan Hora l, Markus A. Kuczyk m, Axel S. Merseburger n, Thomas Powles o, Michael Staehler p, Alessandro Volpe q,Bo¨rje Ljungberg r, Axel Bex s,* a Department of Urology, Cabuen˜es Hospital, Gijo´n, Spain; b Department of Urology, Sunderby Hospital, Sunderby, Sweden; c Department of Urology, University Hospital Hamburg Eppendorf, Hamburg, Germany; d Department of Urology, Coimbra University Hospital, Coimbra, Portugal; e Academic Urology Unit, University of Aberdeen, Aberdeen, UK; f Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; g Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France; h Department of Urology, University of Rennes, Rennes, France; i Division of Urology, University of Texas Medical School at Houston, Houston, TX, USA; j Department of Urology, Ska˚ne University Hospital, Malmo¨, Sweden; k Patient Advocate International Kidney Cancer Coalition (IKCC), University Medical Centre Utrecht, Department of Nephrology and Hypertension, Utrecht, The Netherlands; l Department of Urology, Faculty Hospital
    [Show full text]
  • Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
    Published OnlineFirst September 20, 2013; DOI: 10.1158/2159-8290.CD-13-0350 RESEARCH ARTICLE Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia Tea Pemovska 1 , Mika Kontro 2 , Bhagwan Yadav 1 , Henrik Edgren 1 , Samuli Eldfors1 , Agnieszka Szwajda 1 , Henrikki Almusa 1 , Maxim M. Bespalov 1 , Pekka Ellonen 1 , Erkki Elonen 2 , Bjørn T. Gjertsen5 , 6 , Riikka Karjalainen 1 , Evgeny Kulesskiy 1 , Sonja Lagström 1 , Anna Lehto 1 , Maija Lepistö1 , Tuija Lundán 3 , Muntasir Mamun Majumder 1 , Jesus M. Lopez Marti 1 , Pirkko Mattila 1 , Astrid Murumägi 1 , Satu Mustjoki 2 , Aino Palva 1 , Alun Parsons 1 , Tero Pirttinen 4 , Maria E. Rämet 4 , Minna Suvela 1 , Laura Turunen 1 , Imre Västrik 1 , Maija Wolf 1 , Jonathan Knowles 1 , Tero Aittokallio 1 , Caroline A. Heckman 1 , Kimmo Porkka 2 , Olli Kallioniemi 1 , and Krister Wennerberg 1 ABSTRACT We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profi ling and ex vivo drug sensitivity and resistance testing (DSRT) of patients’ cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered fi ve major taxonomic drug-response sub- types based on DSRT profi les, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3 -ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses.
    [Show full text]
  • VEGF) Inhibitors
    Understanding and managing toxicities of vascular endothelial growth factor (VEGF) inhibitors Manuela Schmidinger * Medical University of Vienna, Vienna, Austria 1. Introduction than bevacizumab. Interestingly, the newest VEGFR–tyrosine kinase inhibitor (TKI) tivozanib appears to have little effect Vascular-endothelial growth-factor (receptor) (VEGF)(R)-inhib- on fatigue levels (all grades: up to 18%, grade P3: 5%). iting agents – sunitinib [1–3], sorafenib [4,5], pazopanib [2,6], Gastrointestinal side-effects are extremely common in pa- bevacizumab [7,8], axitinib [5] and tivozanib [9,10] –have tients on VEGFR–TKI treatment. In particular, sunitinib and changed the therapeutic landscape in metastatic renal-cell axitinib were shown to cause reduced appetite and/or anorex- carcinoma (mRCC). Five out of six agents have been approved ia in up to 34% of the patients. In the case of sunitinib, this for either first-line (sunitinib, pazopanib and bev- may be caused partly by the high incidence of stomatitis acizumab + interferon-alpha) or second-line (sorafenib, axiti- and/or dysgeusia (30% and 46%, respectively). Diarrhoea is an- nib) treatment of metastatic or advanced RCC. With these other frequent gastrointestinal toxicity: high incidences of all novel strategies, the median overall survival of patients has grades of diarrhoea were reported from patients on sunitinib increased considerably, often, however, at the expense of (61%), sorafenib (53%), pazopanib (63%) and axitinib 55%, chronic side-effects. Common treatment-related side-effects again with quite a favourable profile for tivozanib (22%). include: (1) general symptoms such as fatigue and asthenia, The most common skin toxicities caused by VEGFR inhib- (2) gastrointestinal symptoms such as diarrhoea and stomati- itors are hand–foot syndrome (HFS), skin- and/or hair-depig- tis, (3) skin toxicities, (4) cardiovascular toxicities and (5) a mentation and rash.
    [Show full text]
  • Fotivda (Tivozanib)
    Market Applicability Market GA KY MD NJ NY Applicable X X X X X Fotivda (tivozanib) Override(s) Approval Duration Prior Authorization 1 year Quantity Limit Medications Quantity Limit Fotivda (tivozanib) May be subject to quantity limit APPROVAL CRITERIA Requests for Fotivda (tivozanib) may be approved if the following criteria are met: I. Individual has a diagnosis of relapsed or refractory advanced Renal Cell Carcinoma (RCC); AND II. Individual has received at least two prior systemic therapies; AND III. At least one prior systemic therapy included a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI), such as axitinib, cabozantinib, lenvatinib, sunitinib, or pazopanib (Rini 2020). Key References: 1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.: 2021. URL: http://www.clinicalpharmacology.com. Updated periodically. 2. DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed: March 11, 2021. 3. DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated periodically. 4. Lexi-Comp ONLINE™ with AHFS™, Hudson, Ohio: Lexi-Comp, Inc.; 2021; Updated periodically. 5. Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open- label study. Lancet Oncol. 2020 Jan;21(1):95-104. doi: 10.1016/S1470-2045(19)30735-1. Epub 2019 Dec 3. 6. NCCN Clinical Practice Guidelines in Oncology™. © 2019 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp.
    [Show full text]
  • New Century Health Policy Changes April 2021
    Policy # Drug(s) Type of Change Brief Description of Policy Change new Pepaxto (melphalan flufenamide) n/a n/a new Fotivda (tivozanib) n/a n/a new Cosela (trilaciclib) n/a n/a Add inclusion criteria: NSCLC UM ONC_1089 Libtayo (cemiplimab‐rwlc) Negative change 2.Libtayo (cemiplimab) may be used as montherapy in members with locally advanced, recurrent/metastatic NSCLC, with PD‐L1 ≥ 50%, negative for actionable molecular markers (ALK, EGFR, or ROS‐1) Add inclusion criteria: a.As a part of primary/de�ni�ve/cura�ve‐intent concurrent chemo radia�on (Erbitux + Radia�on) as a single agent for members with a UM ONC_1133 Erbitux (Cetuximab) Positive change contraindication and/or intolerance to cisplatin use OR B.Head and Neck Cancers ‐ For recurrent/metasta�c disease as a single agent, or in combination with chemotherapy. Add inclusion criteria: UM ONC_1133 Erbitux (Cetuximab) Negative change NOTE: Erbitux (cetuximab) + Braftovi (encorafenib) is NCH preferred L1 pathway for second‐line or subsequent therapy in the metastatic setting, for BRAFV600E positive colorectal cancer.. Add inclusion criteria: B.HER‐2 Posi�ve Breast Cancer i.Note #1: For adjuvant (post‐opera�ve) use in members who did not receive neoadjuvant therapy/received neoadjuvant therapy and did not have any residual disease in the breast and/or axillary lymph nodes, Perjeta (pertuzumab) use is restricted to node positive stage II and III disease only. ii.Note #2: Perjeta (pertuzumab) use in the neoadjuvant (pre‐opera�ve) se�ng requires radiographic (e.g., breast MRI, CT) and/or pathologic confirmation of ipsilateral (same side) axillary nodal involvement.
    [Show full text]
  • CELEBRATING 25 YEARS of PROGRESS for PATIENTS for PROGRESS of YEARS 25 CELEBRATING Annual Report 2019 Report Annual
    CELEBRATING 25 YEARS OF PROGRESS FOR PATIENTS FOR PROGRESS YEARS OF 25 CELEBRATING Annual Report 2019 Annual Report Exelixis, Inc. Annual Report 2019 2019 HIGHLIGHTS In 2019, Exelixis marked its 25th anniversary. Our progress during the year highlights how far we’ve come since our early days. More than that, though, it underscores our commitment to pushing scientific and technological boundaries to advance our mission to help cancer patients recover stronger and live longer. As we move through 2020, our team has the same drive and passion for the work as we did when we first opened our doors back in 1994. 610+ employees committed to our mission at year-end 2019, an increase of 27% year over year 12 ongoing or planned trials with label-enabling potential, including four announced in 2019 $1 billion in annual global net revenues for the cabozantinib franchise1 20 ongoingon preclinical programs across ExelixisExxelixis internal disdiscovery and our partners, includingincludi three that ccocouldould reach the clinic this year 4 Commerciallyommerciallymmerciallymerciallyerciallyrciallyciallyiallyallyllyy availablavailablea pprproproduprodproductproducts benefittingttingtingingngg patientsatientstientsientsentsntstlblbi ono a ggloglobal basis 1 Including revenues generated by Ipsen Pharma SAS, our partner in cabozantinib’s global development and commercialization outside of the United States and Japan TO OUR STOCKHOLDERS Before I reflect on our progress in 2019, I want to take a moment to acknowledge the obvious: the coronavirus pandemic is making 2020 a markedly different year for the world, our industry, and for Exelixis. Despite this, I’m confident in our ability to navigate these difficult times and the significant challenges posed by COVID-19. For patients with cancer, continuity of treatment is paramount.
    [Show full text]
  • Single Technology Appraisal Tivozanib for Treating Renal Cell Carcinoma Final Scope, 2017
    Single Technology Appraisal Tivozanib for treating renal cell carcinoma [ID591] Committee Papers © National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content in this publication is owned by multiple parties and may not be re-used without the permission of the relevant copyright owner. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE SINGLE TECHNOLOGY APPRAISAL Tivozanib for treating renal cell carcinoma [ID591] Contents: 1. Pre-Meeting Briefing 2. Final Scope and Final Matrix of Consultees and Commentators 3. Company submission from Eusapharma 4. Clarification letters NICE request to the company for clarification on their submission NICE additional clarification questions Company response to NICE’s request for clarification Company IPCW analysis report Company RPSFT report Additional analysis results Scenario anyalyis results 5. Patient group, professional group and NHS organisation submission from: Kidney Cancer Support Network Kidney Cancer UK Royal College of Physicians on behalf of the NCRI-ACP-RCP-RCR 6. Expert statements from: Professor Peter Clark - NHS commissioning expert statement Dr Paul Nathan - clinical expert statement - nominated by the NCRI- ACP-RCP-RCR Professor John Wagstaff – clinical expert statement - nominated by the EUSA Pharma Lucy Willingale – patient expert statement nominated by the Kidney Cancer UK 7. Evidence Review Group report prepared by BMJ Group Evidence Review Group report Erratum 8. Evidence Review Group report – factual accuracy check Any information supplied to NICE which has been marked as confidential, has been redacted. All personal information has also been redacted. © National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content in this publication is owned by multiple parties and may not be re-used without the permission of the relevant copyright owner.
    [Show full text]
  • Imatinib-Loaded Micelles of Hyaluronic Acid Derivatives For
    Article Cite This: Mol. Pharmaceutics 2018, 15, 5031−5045 pubs.acs.org/molecularpharmaceutics Imatinib-Loaded Micelles of Hyaluronic Acid Derivatives for Potential Treatment of Neovascular Ocular Diseases † † † † § † ‡ Flavia Bongiovì, Calogero Fiorica, Fabio S. Palumbo, Giulia Di Prima, , Gaetano Giammona, , † and Giovanna Pitarresi*, † Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universitàdegli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy ‡ Institute of Biophysics at Palermo, Italian National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy *S Supporting Information ABSTRACT: In this work, new micellar systems able to cross corneal barrier and to improve the permeation of imatinib free base were − prepared and characterized. HA-EDA-C16, HA-EDA-C16 PEG, and − HA-EDA-C16 CRN micelles were synthesized starting from hyalur- onic acid (HA), ethylenediamine (EDA), hexadecyl chains (C16), polyethylene glycol (PEG), or L-carnitine (CRN). These nanocarriers showed optimal particle size and mucoadhesive properties. Imatinib- loaded micelles were able to interact with corneal barrier and to promote imatinib transcorneal permeation and penetration. In addition, a study was conducted to understand the in vitro imatinib inhibitory effect on a choroidal neovascularization process. Imatinib released from polymeric micelles was able to inhibit endothelial cell sprouting and to promote cell tube disruption. KEYWORDS: ocular drug delivery, hyaluronic acid, polymeric micelles, imatinib, transcorneal
    [Show full text]
  • Changing Landscapes in the Treatment of Advanced Renal Cell Carcinoma
    Journal of Nephrology Research Online Submissions: http://www.ghrnet.org/index./jnr/ J. of Nephrology Res. 2016; 2(1): 99-108 doi:10.17554/j.issn.2410-0579.2016.02.16 ISSN 2409-0579 EDITORIAL Changing Landscapes in the Treatment of Advanced Renal Cell Carcinoma Arnab Basu, Jenny J Kim Arnab Basu, Jenny J Kim, Department of Hematology and Oncol- 99-108 Available from: URL: http://www.ghrnet.org/index.php/jnr/ ogy, Taussig Cancer Institute, Cleveland Clinic, the United States article/view/1356 Correspondence to: Jenny J Kim, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, the United INTRODUCTION States Renal Cell Carcinoma is a significant cause of worldwide mortality Email: [email protected] and morbidity. Globally, an estimated 338,000 new cases and Telephone: +82-62-220-6700 Fax: + 82-62-227-1643 144,000 deaths occurred due toRenal Cell Carcinomain 2012[1]. It Received: August 5, 2015 Revised: January 1, 2016 is much more prevalent in regions such as North/EasternEurope. Accepted: January 3, 2016 In the US; incidence is approximately 62,000 cases per year with Published online: April 7, 2016 almost 14,000 deaths[2]. Caucasians and African Americans have a higher incidence in comparison to those of Asian or Pacific Islander ABSTRACT descent[3]. Incidence of renal cell carcinoma continues to grow Historically, advanced renal cell cancer stood as a devastating diagno- globally– perhaps driven by lifestyle risk factors such as smoking sis due to the paucity of systemic therapy options. Cytokine therapy and increasing obesity[4]. The detection and diagnosis of incidentally including high dose IL2 and interferon alpha comprised the mainstay found small renal masses is also showing a large increase, due to the of advanced renal cell cancer treatment with modest benefit.
    [Show full text]
  • 24Fa3c0d4a8650845b1a35e56fe
    www.oncotarget.com Oncotarget, 2020, Vol. 11, (No. 5), pp: 535-549 Research Paper Identification of molecular targets for the targeted treatment of gastric cancer using dasatinib Raquel Carvalho Montenegro1, Alison Howarth2, Alessandro Ceroni2, Vita Fedele2, Batoul Farran3, Felipe Pantoja Mesquita1, Martin Frejno4, Benedict-Tilman Berger5,6, Stephanie Heinzlmeir4,7, Heba Z. Sailem8,9, Roberta Tesch5,6, Daniel Ebner2, Stefan Knapp5,6, Rommel Burbano10, Bernhard Kuster4,7,11 and Susanne Müller5 1Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil 2Novo Nordisk Research Centre Oxford (NNRCO), Discovery Technologies and Genomics, Oxford, UK 3Winship Cancer Institute, Emory University, Atlanta, GA, USA 4Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany 5Structural Genomics Consortium, Buchmann Institute for Life Sciences, Goethe-University Frankfurt, Frankfurt, Germany 6Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Frankfurt, Germany 7German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany 8Institute of Biomedical Engineering, Department of Engineering, University of Oxford, Oxford, UK 9Big Data Institute, University of Oxford, Li Ka Shing Centre for Health Information and Discovery, Old Road Campus Research Building, Oxford, UK 10Ophir Loyola Hospital, Belém, PA, Brazil 11Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technische Universität München, Freising, Germany Correspondence to:
    [Show full text]
  • 5.01.534 Multiple Receptor Tyrosine Kinase Inhibitors
    PHARMACY POLICY – 5.01.534 Multiple Receptor Tyrosine Kinase Inhibitors Effective Date: Aug. 1, 2021 RELATED MEDICAL POLICIES: Last Revised: July 9, 2021 5.01.517 Use of Vascular Endothelial Growth Factor Receptor (VEGF) Inhibitors and Replaces: N/A Other Angiogenesis Inhibitors in Oncology Patients 5.01.518 BCR-ABL Kinase Inhibitors 5.01.544 Prostate Cancer Targeted Therapies 5.01.589 BRAF and MEK Inhibitors 5.01.603 Epidermal Growth Factor Receptor (EGFR) Inhibitors Select a hyperlink below to be directed to that section. POLICY CRITERIA | CODING | RELATED INFORMATION EVIDENCE REVIEW | REFERENCES | HISTORY ∞ Clicking this icon returns you to the hyperlinks menu above. Introduction An enzyme is a chemical messenger. Tyrosine kinases are enzymes within cells. They serve as on/off switches for many of the cells’ functions. One of their most important roles is to help send signals telling a cell to grow. If there is a genetic change that leaves the switch permanently on, cells grow without stopping and tumors form. Multiple tyrosine kinase inhibitors block the “grow” signal in specific types of tumors. This policy discusses when multiple receptor tyrosine kinase inhibitors may be considered medically necessary. Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab.
    [Show full text]