Anticancer Drug-Induced Thyroid Dysfunction
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Tyrosine Kinase Inhibitors and Modifications of Thyroid Function Tests
European Journal of Endocrinology (2009) 160 331–336 ISSN 0804-4643 REVIEW Tyrosine kinase inhibitors and modifications of thyroid function tests: a review Fre´de´ric Illouz1,2, Sandrine Laboureau-Soares1,Se´verine Dubois1, Vincent Rohmer1,2,3,4 and Patrice Rodien1,2,3,4 1CHU d’Angers, De´partement d’Endocrinologie Diabe´tologie Nutrition, Angers Cedex 09 F-49933, France, 2Centre de Re´fe´rence des Pathologies de la Re´ceptivite´ Hormonale, CHU d’Angers, Angers Cedex 09 F-49933, France, 3INSERM, U694, Angers Cedex 09 F-49933, France and 4Universite´ d’Angers, Angers Cedex 09 F-49933, France (Correspondence should be addressed to F Illouz; Email: [email protected]) Abstract Tyrosine kinase inhibitors (TKI) belong to new molecular multi-targeted therapies that are approved for the treatment of haematological and solid tumours. They interact with a large variety of protein tyrosine kinases involved in oncogenesis. In 2005, the first case of hypothyroidism was described and since then, some data have been published and have confirmed that TKI can affect the thyroid function tests (TFT). This review analyses the present clinical and fundamental findings about the effects of TKI on the thyroid function. Various hypotheses have been proposed to explain the effect of TKI on the thyroid function but those are mainly based on clinical observations. Moreover, it appears that TKI could alter the thyroid hormone regulation by mechanisms that are specific to each molecule. The present propositions for the management of TKI-induced hypothyroidism suggest that we assess the TFT of the patients regularly before and during the treatment by TKI. -
PD-L1 Expression and Clinical Outcomes to Cabozantinib
Author Manuscript Published OnlineFirst on August 1, 2019; DOI: 10.1158/1078-0432.CCR-19-1135 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. PD-L1 expression and clinical outcomes to cabozantinib, everolimus and sunitinib in patients with metastatic renal cell carcinoma: analysis of the randomized clinical trials METEOR and CABOSUN Abdallah Flaifel1, Wanling Xie2, David A. Braun3, Miriam Ficial1, Ziad Bakouny3, Amin H. Nassar3, Rebecca B. Jennings1, Bernard Escudier4, Daniel J. George5, Robert J. Motzer6, Michael J. Morris6, Thomas Powles7, Evelyn Wang8, Ying Huang9, Gordon J. Freeman3, Toni K. Choueiri*3, Sabina Signoretti*1,9 1Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 2Department of Data Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA 3Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA 4Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France 5Department Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA 6Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA 7Department of Experimental Cancer Medicine, Barts Cancer Institute, London, UK 8Exelixis Inc., South San Francisco, CA, USA 9Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA *equal contribution Correspondence: Toni K. Choueiri, M.D., Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 1230, 450 Brookline Ave, Boston, MA 02115; Phone: 617-632-5456; Fax: 617-632-2165 E-mail: [email protected] Or Sabina Signoretti, M.D., Department of Pathology, Brigham and Women's Hospital, Thorn Building 504A, 75 Francis Street, Boston, MA 02115; Phone: 617-525-7437; Fax: 617-264-5169 Email: [email protected] Downloaded from clincancerres.aacrjournals.org on September 29, 2021. -
Management of Brain and Leptomeningeal Metastases from Breast Cancer
International Journal of Molecular Sciences Review Management of Brain and Leptomeningeal Metastases from Breast Cancer Alessia Pellerino 1,* , Valeria Internò 2 , Francesca Mo 1, Federica Franchino 1, Riccardo Soffietti 1 and Roberta Rudà 1,3 1 Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy; [email protected] (F.M.); [email protected] (F.F.); riccardo.soffi[email protected] (R.S.); [email protected] (R.R.) 2 Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, 70121 Bari, Italy; [email protected] 3 Department of Neurology, Castelfranco Veneto and Treviso Hospital, 31100 Treviso, Italy * Correspondence: [email protected]; Tel.: +39-011-6334904 Received: 11 September 2020; Accepted: 10 November 2020; Published: 12 November 2020 Abstract: The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians. Some prognostic scales designed for metastatic BC have been employed to select fit patients for adequate therapy and enrollment in clinical trials. Different systemic drugs, such as targeted therapies with either monoclonal antibodies or small tyrosine kinase molecules, or modified chemotherapeutic agents are under investigation. Major aims are to improve the penetration of active drugs through the blood–brain barrier (BBB) or brain–tumor barrier (BTB), and establish the best sequence and timing of radiotherapy and systemic therapy to avoid neurocognitive impairment. Moreover, pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. -
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. -
BC Cancer Benefit Drug List September 2021
Page 1 of 65 BC Cancer Benefit Drug List September 2021 DEFINITIONS Class I Reimbursed for active cancer or approved treatment or approved indication only. Reimbursed for approved indications only. Completion of the BC Cancer Compassionate Access Program Application (formerly Undesignated Indication Form) is necessary to Restricted Funding (R) provide the appropriate clinical information for each patient. NOTES 1. BC Cancer will reimburse, to the Communities Oncology Network hospital pharmacy, the actual acquisition cost of a Benefit Drug, up to the maximum price as determined by BC Cancer, based on the current brand and contract price. Please contact the OSCAR Hotline at 1-888-355-0355 if more information is required. 2. Not Otherwise Specified (NOS) code only applicable to Class I drugs where indicated. 3. Intrahepatic use of chemotherapy drugs is not reimbursable unless specified. 4. For queries regarding other indications not specified, please contact the BC Cancer Compassionate Access Program Office at 604.877.6000 x 6277 or [email protected] DOSAGE TUMOUR PROTOCOL DRUG APPROVED INDICATIONS CLASS NOTES FORM SITE CODES Therapy for Metastatic Castration-Sensitive Prostate Cancer using abiraterone tablet Genitourinary UGUMCSPABI* R Abiraterone and Prednisone Palliative Therapy for Metastatic Castration Resistant Prostate Cancer abiraterone tablet Genitourinary UGUPABI R Using Abiraterone and prednisone acitretin capsule Lymphoma reversal of early dysplastic and neoplastic stem changes LYNOS I first-line treatment of epidermal -
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. -
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 -
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. -
TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage . -
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. -
Phase II Study of Motesanib in Japanese Patients with Advanced Gastrointestinal Stromal Tumors with Prior Exposure to Imatinib Mesylate
Cancer Chemother Pharmacol (2010) 65:961–967 DOI 10.1007/s00280-009-1103-9 ORIGINAL ARTICLE Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate Akira Sawaki · Yasuhide Yamada · Yoshito Komatsu · Tatsuo Kanda · Toshihiko Doi · Masato Koseki · Hideo Baba · Yu-Nien Sun · Koji Murakami · Toshirou Nishida Received: 24 May 2009 / Accepted: 29 July 2009 / Published online: 19 August 2009 © The Author(s) 2009. This article is published with open access at Springerlink.com Abstract according to the Common Terminology Criteria for Purpose Motesanib (AMG 706) is a multitargeted anti- Adverse Events (version 3). cancer agent with an inhibitory action on the human vascu- Results Of 35 enrolled and treated patients, no patient lar endothelial growth factor receptor, the platelet-derived showed a complete response, and one patient showed a par- growth factor receptor, and the cellular stem-cell factor tial response (PR). Seven had stable disease (SD) for at receptor (KIT). The aim of this single-arm phase II clinical least 24 months, two of whom continued to have SD for study was to assess the eYcacy and safety of single-agent more than 2 years. The median progression-free survival motesanib in Japanese patients with advanced gastrointesti- time was 16.1 weeks. Motesanib was well tolerated; com- nal stromal tumors with prior exposure to imatinib monly reported treatment-related adverse events were mesylate. hypertension, diarrhea, and fatigue. Anemia was the only Methods All patients had experienced progression or hematological toxicity that was reported. relapse while undergoing with imatinib as 400 mg/day or Conclusions One patient showed PR, and seven patients higher. -
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.