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Bosutinib

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https://www.readbyqxmd.com/read/28807791/effects-of-bosutinib-treatment-on-renal-function-in-patients-with-philadelphia-chromosome-positive-leukemias
#1
Jorge E Cortes, Carlo Gambacorti-Passerini, Dong-Wook Kim, Hagop M Kantarjian, Jeff H Lipton, Amit Lahoti, Moshe Talpaz, Ewa Matczak, Elly Barry, Eric Leip, Tim H Brümmendorf, H Jean Khoury
BACKGROUND: The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. PATIENTS AND METHODS: Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. RESULTS: Time from the last patient's first dose to data cutoff was ≥ 48 months...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#2
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28774214/the-safety-of-bosutinib-for-the-treatment-of-chronic-myeloid-leukemia
#3
Jee Hyun Kong, H J Khoury, Audrey Sunwha Kim, Brittany Gray Hill, Vamsi Kota
Introduction Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy...
August 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28756527/synergistic-tumor-suppression-by-a-perilla-frutescens-derived-methoxyflavanone-and-anti-cancer-tyrosine-kinase-inhibitors-in-a549-human-lung-adenocarcinoma
#4
Amer Ali Abd El-Hafeez, Takashi Fujimura, Rikiya Kamei, Noriko Hirakawa, Kenji Baba, Kazuhisa Ono, Seiji Kawamoto
Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of cancers including non-small cell lung cancer, while appearance of TKI-resistant tumors suggests a need for the development of their potentiation strategies. We have previously shown that a methoxyflavanone derivative from the Asian medicinal herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and ponatinib) synergistically suppress proliferation of A549 cells...
July 29, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28639957/pulmonary-arterial-hypertension-induced-by-tyrosine-kinase-inhibitors
#5
Jason Weatherald, Marie-Camille Chaumais, David Montani
PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several neoplastic conditions; however, pulmonary arterial hypertension (PAH) has been reported as a complication of TKIs, predominantly with dasatinib. Recent studies have elucidated the potential mechanisms of TKI-induced PAH and have better clarified the long-term outcomes. RECENT FINDINGS: In addition to the known association between dasatinib and PAH, several other TKIs have recently been reported to cause PAH, including ponatinib, bosutinib and lapatinib...
September 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28637715/tyrosine-kinase-inhibitors-protect-the-salivary-gland-from-radiation-damage-by-inhibiting-activation-of-protein-kinase-c-%C3%AE
#6
Sten M Wie, Elizabeth Wellberg, Sana D Karam, Mary E Reyland
In patients undergoing irradiation therapy, injury to non-tumor tissues can result in debilitating, and sometimes permanent, side effects. We have defined Protein Kinase C-delta (PKCδ) as a regulator of DNA damage induced apoptosis and have shown that phosphorylation of PKCδ by c-Abl and c-Src activates its pro-apoptotic function.  Here we have explored the use of tyrosine kinase inhibitors (TKIs) of c-Src and c-Abl to block activation of PKCδ for radioprotection of the salivary gland.  Dasatinib, imatinib, and bosutinib all suppressed tyrosine phosphorylation of PKCδ and inhibited IR-induced apoptosis in vitro  To determine if TKIs can provide radioprotection of salivary gland function in vivo, mice were treated with TKIs and a single or fractionated doses of irradiation...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28599428/bosutinib-as-a-fourth-line-therapy-for-a-patient-with-t315i-positive-lymphoid-blastic-phase-chronic-myeloid-leukemia-a-case-report
#7
Yukiko Komeno, Naoyuki Uchida, Yumiko Satoh, Hideki Uryu, Yuko Iwata, Akiko Masuda, Kuniko Iihara, Yutaka Yatomi, Shuichi Taniguchi, Tomiko Ryu
A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28560147/bosutinib-induced-pleural-effusions-case-report-and-review-of-tyrosine-kinase-inhibitors-induced-pulmonary-toxicity
#8
Natalia I Moguillansky, Hafiz Abdul Moiz Fakih, John R Wingard
Tyrosine kinase inhibitors are known to cause pulmonary complications. We report a case of bosutinib related bilateral pleural effusions in a patient with chronic myeloid leukemia. Characteristics of the pleural fluid are presented. We also discuss other tyrosine kinase inhibitors induced pulmonary toxicities, including pulmonary hypertension and interstitial lung disease.
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#9
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28475010/computational-analysis-of-abl-kinase-mutations-allows-predicting-drug-sensitivity-against-selective-kinase-inhibitors
#10
Swapna Kamasani, Sravani Akula, Sree Kanth Sivan, Vijjulatha Manga, Justus Duyster, Dashavantha Reddy Vudem, Rama Krishna Kancha
The ABL kinase inhibitor imatinib has been used as front-line therapy for Philadelphia-positive chronic myeloid leukemia. However, a significant proportion of imatinib-treated patients relapse due to occurrence of mutations in the ABL kinase domain. Although inhibitor sensitivity for a set of mutations was reported, the role of less frequent ABL kinase mutations in drug sensitivity/resistance is not known. Moreover, recent reports indicate distinct resistance profiles for second-generation ABL inhibitors. We thus employed a computational approach to predict drug sensitivity of 234 point mutations that were reported in chronic myeloid leukemia patients...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28470980/aprepitant-and-fosaprepitant-drug-interactions-a-systematic-review
#11
Priya Patel, J Steven Leeder, Micheline Piquette-Miller, L Lee Dupuis
AIMS: Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant. METHODS: We systematically reviewed the literature to September 11, 2016 to identify articles evaluating drug interactions involving aprepitant/fosaprepitant...
May 4, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28416739/tki-rotation-induced-persistent-deep-molecular-response-in-multi-resistant-blast-crisis-of-ph-cml
#12
Peter Valent, Susanne Herndlhofer, Mathias Schneeweiß, Bernd Boidol, Anna Ringler, Stefan Kubicek, Karoline V Gleixner, Gregor Hoermann, Emir Hadzijusufovic, Leonhard Müllauer, Wolfgang R Sperr, Giulio Superti-Furga, Christine Mannhalter
In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1 tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data suggest that TKI combinations may overcome resistance. We report on a heavily pre-treated 78 year-old female patient with CML who developed multi-resistant blast crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR-ABL1, but also in severe thrombocytopenia with bleedings requiring platelet transfusions...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409328/long-term-treatment-with-bosutinib-in-a-phase-1-2-study-in-japanese-chronic-myeloid-leukemia-patients-resistant-intolerant-to-prior-tyrosine-kinase-inhibitor-treatment
#13
Naoto Takahashi, Chiaki Nakaseko, Yukio Kobayashi, Koichi Miyamura, Chiho Ono, Yuichiro Koide, Yosuke Fujii, Kazunori Ohnishi
This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3‒372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively...
April 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28377326/treatment-and-molecular-monitoring-update-in-chronic-myeloid-leukemia-management
#14
Nathalie Sorel, Émilie Cayssials, Françoise Brizard, Jean-Claude Chomel
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the t(9;22)(q34;q11) translocation. It is characterized by the presence of the BCR-ABL1 fusion gene encoding the BCR-ABL oncoprotein characterized by a deregulated tyrosine kinase activity. Targeted therapies using tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib, bosutinib, or ponatinib have profoundly changed the natural history of the disease with a major impact on survival. Indeed, most patients diagnosed today can enjoy a near normal life expectancy...
April 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28374910/a-quantitative-method-for-the-determination-of-bosutinib-in-human-plasma-using-high-performance-liquid-chromatography-and-ultraviolet-detection
#15
Takahiro Sumimoto, Ryosuke Nakahara, Yuhki Sato, Hiroki Itoh
BACKGROUND: We propose a simple, sensitive, and fast high-performance liquid chromatography ultraviolet detection (HPLC-UV) method for the quantitative determination of bosutinib in human plasma. METHODS: Plasma samples were processed using an Oasis hydrophilic-lipophilic balance extraction cartridge (1 mL, 30 mg). Bosutinib and the internal standard imatinib were separated using a mobile phase of 0.5% Na2 PO4 H2 O (pH 3.5)-acetonitrile-methanol (55:25:20, v/v/v) on a CAPCELL PAK C18 MG II reversed-phase column 250 nm×4...
April 4, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28371355/bosutinib-an-src-inhibitor-induces-caspase-independent-cell-death-associated-with-permeabilization-of-lysosomal-membranes-in-melanoma-cells
#16
S Noguchi, S Shibutani, K Fukushima, T Mori, M Igase, T Mizuno
BACKGROUND: SRC kinase (SRC proto-oncogene, non-receptor tyrosine kinase) is a promising target for the treatment of solid cancers including human melanoma. Bosutinib (Bosu), a SRC inhibitor, has already been applied to the treatment of human chronic myelogenous leukemia and also has been assessed its safety in dogs. AIM: The aim of this study was to clarify a novel anti-tumour mechanism of Bosu in canine and human melanoma cells. MATERIALS AND METHODS: The canine and human melanoma cells were treated with Bosu and its effects were evaluated by the cell viability, the protein expression levels such as caspase-3 and LC3, Annexin V/Propidium iodide staining, and confocal immunostaining...
March 28, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28360865/bosutinib-therapy-ameliorates-lung-inflammation-and-fibrosis-in-experimental-silicosis
#17
Priscila J Carneiro, Amanda L Clevelario, Gisele A Padilha, Johnatas D Silva, Jamil Z Kitoko, Priscilla C Olsen, Vera L Capelozzi, Patricia R M Rocco, Fernanda F Cruz
Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#18
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation, and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDIs). The objective of this work is to determine if the transgenic (Tg) Cyp3a(-/-)Tg-3A4Hep/Int and Nr1i2/Nr1i3(-/-)-Cyp3a(-/-)Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims); with varying magnitudes of reported CYP3A4 clinical DDI...
April 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#19
Hanna L M Rajala, Mohamed El Missiry, Anniina Ruusila, Perttu Koskenvesa, Tim H Brümmendorf, Bjorn T Gjertsen, Jeroen Janssen, Kourosh Lotfi, Berit Markevärn, Ulla Olsson-Strömberg, Leif Stenke, Jesper Stentoft, Johan Richter, Henrik Hjorth-Hansen, Anna Kreutzman, Satu Mustjoki
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment...
August 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28316033/cardiovascular-complications-of-targeted-therapies-for-chronic-myeloid-leukemia
#20
REVIEW
Rongras Damrongwatanasuk, Michael G Fradley
The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib...
April 2017: Current Treatment Options in Cardiovascular Medicine
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