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Nilotinib

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https://www.readbyqxmd.com/read/29665906/-imatinib-as-second-line-treatment-drug-for-cml-patients-intolerant-to-nilotinib
#1
Jing Qi, You-Hai Xu, He-Sheng He
OBJECTIVE: To explore the individualized treatment for patient with chronic phase chronic myeloid leukemia(CML-CP). METHODS: The clinical data and treatment process of one CML-CP patient which intolerated to nilotinib were analyzed. RESULTS: Nilotinib was given to the patient once the diagnosis of CML-CP was set. Although major molecular remission (MMR) and complete cytogenetic remission (CCyR) were obtained during treatment for 3 months, a grade 3-4 hepatotoxicity appeared in the course of treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660177/severe-adverse-events-by-tyrosine-kinase-inhibitors-decrease-survival-rates-in-patients-with-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#2
Shuichi Ota, Toshihiro Matsukawa, Satoshi Yamamoto, Ito Shinichi, Motohiro Shindo, Kazuya Sato, Takeshi Kondo, Kyuhei Kohda, Hajime Sakai, Akio Mori, Tohru Takahashi, Hiroshi Ikeda, Hiroyuki Kuroda, Yoshihito Haseyama, Masaki Yamamoto, Takeo Sarashina, Makoto Yoshida, Ryoji Kobayashi, Mitsufumi Nishio, Toshimichi Ishihara, Yasuo Hirayama, Yasutaka Kakinoki, Hajime Kobayashi, Takashi Fukuhara, Masahiro Imamura, Mitsutoshi Kurosawa
OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89...
April 16, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29643146/fda-expands-indication-for-nilotinib
#3
(no author information available yet)
The FDA expanded the indication for nilotinib for the treatment of children with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase who are at least a year old, as well as those who are resistant to or cannot tolerate imatinib. The drug is the third tyrosine kinase inhibitor approved for children with this rare cancer.
April 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29625098/evaluation-of-kinase-inhibitors-nilotinib-and-everolimus-against-alveolar-echinococcosis-in-vitro-and-in-a-mouse-model
#4
Deborah E Joekel, Britta Lundström-Stadelmann, Beat Müllhaupt, Andrew Hemphill, Peter Deplazes
Infection with the larval stage (metacestode) of the fox tapeworm Echinococcus multilocularis leads to a primary hepatic disease referred to as alveolar echinococcosis (AE). The progressive disease can be lethal if untreated. In cases where complete parasite resection by surgery is not feasible, the current treatment regimens of AE consist of chemotherapy with the parasitostatic benzimidazoles albendazole or mebendazole over decades. Kinase-inhibitors currently administered in various cancer treatments are of increasing interest also as anti-parasitic drugs due to previous promising in vitro results...
April 3, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29620650/durable-remission-in-a-patient-of-mixed-phenotype-acute-leukemia-with-philadelphia-chromosome-positive-treated-with-nilotinib-and-lenalidomide-a-case-report
#5
Binbin Lai, Qitian Mu, Huiling Zhu, Yi Wang, Yi Zhang, Kaihong Xu, Lixia Sheng, Guifang Ouyang
RATIONALE: Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph+ MPAL) is a rare type of leukemia with poor prognosis. Tyrosine kinase inhibitors (TKIs) in combination with chemotherapy have significantly improved its remission rate. However, relapse remains the major obstacle to achieve long survival. Lenalidomide is a second-generation oral immunomodulatory drug that has been broadly applied in the treatment of various hematological malignancies. PATIENT CONCERNS: A 54-year-old Chinese male patient who complained of chest pain and fatigue for 20 days...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29616409/cardiotoxicity-in-hematological-diseases-are-the-tyrosine-kinase-inhibitors-imatinib-and-nilotinib-safe
#6
Ana Rita G Francisco, Daniela Alves, Cláudio David, Lurdes Guerra, Fausto J Pinto, Ana G Almeida
Chemotherapy-induced cardiotoxicity is a growing concern. The cardiotoxic impact of new drugs such as tyrosine kinase inhibitors is unknown, especially the ones used for chronic myeloid leukemia. We aim to evaluate nilotinib- and imatinib-induced cardiotoxicity. Single-center prospective study of consecutive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors was conducted during 2015. Patients underwent an initial clinical, laboratorial and echocardiographic evaluation, repeated after 1 year...
April 3, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29610029/final-3-year-results-of-the-dasatinib-discontinuation-trial-in-patients-with-chronic-myeloid-leukemia-who-received-dasatinib-as-a-second-line-treatment
#7
Masaya Okada, Jun Imagawa, Hideo Tanaka, Hirohisa Nakamae, Masayuki Hino, Kazunori Murai, Yoji Ishida, Takashi Kumagai, Seiichi Sato, Kazuteru Ohashi, Hisashi Sakamaki, Hisashi Wakita, Nobuhiko Uoshima, Yasunori Nakagawa, Yosuke Minami, Masahiro Ogasawara, Tomoharu Takeoka, Hiroshi Akasaka, Takahiko Utsumi, Naokuni Uike, Tsutomu Sato, Sachiko Ando, Kensuke Usuki, Syuichi Mizuta, Satoshi Hashino, Tetsuhiko Nomura, Masato Shikami, Hisashi Fukutani, Yokiko Ohe, Hiroshi Kosugi, Hirohiko Shibayama, Yasuhiro Maeda, Toshihiro Fukushima, Hirohito Yamazaki, Kazuo Tsubaki, Toshimasa Kukita, Yoko Adachi, Toshiki Nataduka, Hiroto Sakoda, Hisayuki Yokoyama, Takahiro Okamoto, Yukari Shirasugi, Yasushi Onishi, Masaharu Nohgawa, Satoshi Yoshihara, Satoshi Morita, Junichi Sakamoto, Shinya Kimura
INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan...
March 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29609532/design-and-rationale-for-the-life-after-stopping-tyrosine-kinase-inhibitors-last-study-a-prospective-single-group-longitudinal-study-in-patients-with-chronic-myeloid-leukemia
#8
Ehab Atallah, Charles A Schiffer, Kevin P Weinfurt, Mei-Jie Zhang, Jerald P Radich, Vivian G Oehler, Javier Pinilla-Ibarz, Michael W N Deininger, Li Lin, Richard A Larson, Michael J Mauro, Joseph O Moore, Ellen K Ritchie, Neil P Shah, Richard T Silver, Martha Wadleigh, Jorge Cortes, James Thompson, Jessica Guhl, Mary M Horowitz, Kathryn E Flynn
BACKGROUND: Treatment of chronic myeloid leukemia with a tyrosine kinase inhibitor (TKI) offers significant improvements over previous treatments in terms of survival and toxicity yet nevertheless is associated with reduced health-related quality of life and very high cost. Several small studies from Europe and Australia suggested that discontinuing TKIs with regular monitoring was safe. METHODS: The Life After Stopping TKIs (LAST) study is a large, U.S.-based study that aims to improve the evidence for clinical decision making regarding TKI discontinuation with monitoring in patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29600692/the-window-of-opportunities-for-targeted-therapy-in-brafwt-nraswt-kitwt-melanoma-biology-and-clinical-implications-of-fusion-proteins-and-other-mutations
#9
Marina Berger, Georg Richtig, Karl Kashofer, Ariane Aigelsreiter, Erika Richtig
Treatment options in advanced melanoma have been subject to a major change over the last years. The discovery of the oncogenic point mutation BRAFV600E and subsequently developed BRAF inhibitors had a major impact on patient's survival. Further important mutations have been found in the NRAS gene, although not yet druggable, and others involve c-kit in acral and mucosal melanoma. Imatinib was shown to achieve high response rates in c-kit mutated melanoma. Despite good response rates in these targeted therapies and introduction of immunotherapy, there are still patients left, who develop resistance upon therapy or patients without the option of targeted therapy...
March 29, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/29581839/excellent-outcomes-of-2g-tki-therapy-after-imatinib-failure-in-chronic-phase-cml-patients
#10
Mario Tiribelli, Massimiliano Bonifacio, Gianni Binotto, Alessandra Iurlo, Francesca Cibien, Elena Maino, Anna Guella, Gianluca Festini, Claudia Minotto, Ercole De Biasi, Federico De Marchi, Luigi Scaffidi, Luca Frison, Cristina Bucelli, Marta Medeot, Elisabetta Calistri, Rosaria Sancetta, Manuela Stulle, Nicola Orofino, Mauro Krampera, Filippo Gherlinzoni, Gianpietro Semenzato, Giovanni Pizzolo, Achille Ambrosetti, Renato Fanin
Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib ( n = 95) or nilotinib ( n = 68) as second-line therapy after imatinib...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29577674/a-phase-4-study-of-nilotinib-in-korean-patients-with-philadelphia-chromosome-positive-chronic-myeloid-leukemia-in-chronic-phase-enestkorea
#11
Junghoon Shin, Youngil Koh, Seo Hyun Yoon, Joo-Youn Cho, Dae-Young Kim, Kyoo-Hyung Lee, Hyeong-Joon Kim, Jae-Sook Ahn, Yeo-Kyeoung Kim, Jinny Park, Sang-Kyun Sohn, Joon Ho Moon, Yoo Jin Lee, Seonghae Yoon, Jeong-Ok Lee, June-Won Cheong, Kyoung Ha Kim, Sung-Hyun Kim, Hoon-Gu Kim, Hawk Kim, Seung-Hyun Nam, Young Rok Do, Sang-Gon Park, Seong Kyu Park, Sung Hwa Bae, Hun Ho Song, Dong-Yeop Shin, Doyeun Oh, Min Kyoung Kim, Chul Won Jung, Seonyang Park, Inho Kim
Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML-CP). We investigated the 2-year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open-label, multi-institutional phase 4 study, 110 Philadelphia chromosome-positive CML-CP patients were treated with nilotinib at a starting dose of 300 mg twice daily...
March 25, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29571947/nilotinib-in-locally-advanced-pigmented-villonodular-synovitis-challenges-of-a-new-targeted-therapy
#12
Francois Gouin
No abstract text is available yet for this article.
March 20, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29571946/nilotinib-in-locally-advanced-pigmented-villonodular-synovitis-a-multicentre-open-label-single-arm-phase-2-trial
#13
Hans Gelderblom, Claire Cropet, Christine Chevreau, Richard Boyle, Martin Tattersall, Silvia Stacchiotti, Antoine Italiano, Sophie Piperno-Neumann, Axel Le Cesne, Virginia Ferraresi, Nicolas Penel, Florence Duffaud, Philippe Cassier, Maud Toulmonde, Paolo Casali, Sophie Taieb, Séverine Guillemaut, Séverine Metzger, David Pérol, Jean-Yves Blay
BACKGROUND: Pigmented villonodular synovitis (alternatively known as diffuse-type giant cell tumour) is a rare, locally aggressive tumour driven by a specific translocation resulting in the overexpression of colony-stimulating factor 1 (CSF1). CSF1 receptor (CSF1R) inhibitors (ie, tyrosine kinase inhibitors and antibodies) induce a response in patients with pigmented villonodular synovitis. We investigated the safety and efficacy of a CSF1R tyrosine kinase inhibitor, nilotinib, in patients with locally advanced non-resectable pigmented villonodular synovitis...
March 20, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29568367/the-new-allosteric-inhibitor-asciminib-is-susceptible-to-resistance-mediated-by-abcb1-and-abcg2-overexpression-in-vitro
#14
Laura N Eadie, Verity A Saunders, Susan Branford, Deborah L White, Timothy P Hughes
Asciminib (previously ABL001), which binds the myristate-binding pocket of the Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in combination with imatinib, nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL. Asciminib sensitivity was evaluated in asciminib naïve BCR-ABL1+ cell lines K562 (negligible ABCB1/ABCG2 expression), K562-Dox (ABCB1-overexpressing through doxorubicin exposure) and K562-ABCG2 (ABCG2 overexpression via transduction) with results demonstrating asciminib efflux by both ABCB1 and ABCG2 transporters...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29567798/ponatinib-efficacy-and-safety-in-philadelphia-chromosome-positive-leukemia-final-5-year-results-of-the-phase-2-pace-trial
#15
Jorge E Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D le Coutre, Ronald Paquette, Charles Chuah, Franck E Nicolini, Jane F Apperley, H Jean Khoury, Moshe Talpaz, Daniel J DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C Müller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Victor M Rivera, Frank G Haluska, François Guilhot, Michael W Deininger, Andreas Hochhaus, Timothy P Hughes, Neil P Shah, Hagop M Kantarjian
Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I The pivotal phase 2 PACE trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to dasatinib or nilotinib, or with BCR ABL1T315I This analysis focuses on chronic-phase CML (CP-CML) patients (n=270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and MR4...
March 22, 2018: Blood
https://www.readbyqxmd.com/read/29562444/-efficacy-comparison-of-sequential-treatment-with-first-line-administration-of-second-generation-and-first-generation-tyrosine-kinase-inhibitors-in-patients-with-ph-acute-lymphoblastic-leukemia-followed-by-allogeneic-hematopoietic-stem-cell-transplantation
#16
F Yang, W Z Cai, X D Yang, S N Chen, X W Tang, A N Sun, D P Wu, W Q Qian, H Y Qiu
Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph+ ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29549292/prospective-evaluation-of-sequential-treatment-of-sclerotic-chronic-graft-versus-host-disease-with-rituximab-and-nilotinib
#17
Lotte van der Wagen, Liane Te Boome, Marleen Schiffler, Inger Nijhof, Marieke Schoordijk, Suzanne van Dorp, Marijke van Dijk, Reinier Raymakers, Eefke Petersen, Moniek de Witte, Niels de Jong, Mar Bellido, Brigitte Bär, Ellen Meijer, Jürgen Kuball
Sclerotic chronic graft vs. host disease (cGVHD) still has a large impact on morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). We performed the first prospective study to test whether sequential therapy of the anti-CD20 antibody rituximab followed by 6 months treatment with tyrosine kinase inhibitor nilotinib is a favorable treatment strategy for patients with sclerotic cGVHD. Twenty-nine patients were included, 24 were available for analysis. We observed objective responses in 71% of patients (two patients CR, 15 patients PR)...
March 16, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29545424/chronic-myelogenous-leukaemia-with-a-p53-mutation-demonstrated-neutrophilic-granulocytes-with-nuclear-hypolobation-pseudo-pelger-h%C3%A3-et-anomaly-and-hypogranulation-in-the-peripheral-blood-smear
#18
Motoharu Shibusawa, Jiro Tadokoro, Masaru Kojima, Makoto Kashimura
A 70-year-old man visited our emergency department, whose laboratory test results revealed leucocytosis, anaemia, thrombocytopenia and high levels of serum lactate dehydrogenase. In addition, the peripheral blood smear revealed neutrophilic granulocytes with nuclear hypolobation (pseudo-Pelger-Hüet anomaly), hypogranulation and no myeloperoxidase reactivity. Genetic testing of the peripheral blood sample was as follows: G-band, 46XY,t(9;22)(q34;q11.2) (20/20); fluorescence in situ hybridisation BCR/ABL fusion signal, 97%; and analysis of exons 5-9 of the p53 gene, mutation (Pro72Arg) in exon 4 protein...
March 15, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29531660/safety-and-efficacy-of-nilotinib-in-routine-clinical-practice-in-patients-with-chronic-myeloid-leukemia-in-chronic-or-accelerated-phase-with-resistance-or-intolerance-to-imatinib-results-from-the-novel-study
#19
Ching-Yuan Kuo, Po-Nan Wang, Wen-Li Hwang, Cheng-Hwai Tzeng, Li-Yaun Bai, Jih-Luh Tang, Ming-Chih Chang, Sheng-Fung Lin, Tsai-Yun Chen, Yeu-Chin Chen, Tran-Der Tan, Chih-Yi Hsieh, Chinjune Lin, Clinton Lai, Darko Miljkovic, Cheng-Shyong Chang
Background: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. Methods: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs...
March 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29519619/efficacy-of-ponatinib-versus-earlier-generation-tyrosine-kinase-inhibitors-for-front-line-treatment-of-newly-diagnosed-philadelphia-positive-acute-lymphoblastic-leukemia
#20
Elias Jabbour, Maral DerSarkissian, Mei Sheng Duh, Nora McCormick, Wendy Y Cheng, Lisa J McGarry, Ariadne Souroutzidis, Hui Huang, Susan O'Brien, Farhad Ravandi, Hagop M Kantarjian
INTRODUCTION: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). PATIENTS AND METHODS: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
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