High ‐grade B‐cell lymphoma developed during the treatment of chronic myeloid leukemia with bosutinib
There remains no consensus on the management of secondary lymphoma during TKI therapies. The only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma. AbstractTyrosine kinase inhibitor (TKI) can help to increase the survival time in chronic myeloid leukemia (CML) patients; however, the risk of secondary malignancies due to TKIs is a growing concern. Only few reports showed clinical course of patients who developed lymphoma during TKI therapies. Herein, we report a case of high ‐grade B‐cell lymphoma diagnosed in the course of CML t...
Source: Clinical Case Reports - January 13, 2021 Category: General Medicine Authors: Teruhito Takakuwa, Ryota Sakai, Shiro Koh, Hiroshi Okamura, Satoru Nanno, Yasuhiro Nakashima, Takahiko Nakane, Hideo Koh, Masayuki Hino, Hirohisa Nakamae Tags: CASE REPORT Source Type: research

Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis
Leukemia, Published online: 07 January 2021; doi:10.1038/s41375-020-01111-2Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis (Source: Leukemia)
Source: Leukemia - January 7, 2021 Category: Hematology Authors: Hagop M. Kantarjian Timothy P. Hughes Richard A. Larson Dong-Wook Kim Surapol Issaragrisil Philipp le Coutre Gabriel Etienne Carla Boquimpani Ricardo Pasquini Richard E. Clark Viviane Dubruille Ian W. Flinn Slawomira Kyrcz-Krzemien Ewa Medras Maria Zanich Source Type: research

Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib
AbstractRecommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12  months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels> ...
Source: Annals of Hematology - January 3, 2021 Category: Hematology Source Type: research

Discovery and Protein Modeling Studies of Novel Compound Mutations Causing Resistance to Multiple Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.
CONCLUSION: We report a novel nilotinib resistant BCR-ABL compound mutation (K245N along with G250W mutation) which impacts structural modification in BCR-ABL mutant protein leading to drug resistance. As compound mutations pose a new threat by causing resistance to all FDA approved tyrosine kinase inhibitors in BCR-ABL+ leukemias, our study opens a new direction for in vitro characterization of novel BCR-ABL compound mutations and their resistant to second  generation and third generation TKIs. PMID: 33369447 [PubMed - as supplied by publisher] (Source: Asian Pacific Journal of Cancer Prevention)
Source: Asian Pacific Journal of Cancer Prevention - December 30, 2020 Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research

Nilotinib in Patients With Moderately Advanced Parkinson Disease
This randomized clinical trial assesses safety and tolerability of nilotinib in participants with moderately advanced Parkinson disease. (Source: JAMA Neurology)
Source: JAMA Neurology - December 14, 2020 Category: Neurology Source Type: research

First-generation vs second-generation tyrosine kinase inhibitors: which is best at diagnosis of chronic phase chronic myeloid leukemia?
Authors: Oehler VG Abstract In 2020, for the great majority of patients with chronic phase chronic myeloid leukemia (CML), life expectancy is unaffected by a diagnosis of CML because of the unparalleled efficacy of ABL-targeted tyrosine kinase inhibitors (TKIs) in halting disease progression. A wealth of choices exist for first-line treatment selection, including the first-generation TKI imatinib and the second-generation TKIs bosutinib, dasatinib, and nilotinib. How I select first-line therapy between first-generation and second-generation TKIs is discussed in the context of patient-specific CML disease risk, ther...
Source: Hematology ASH Education Program - December 5, 2020 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

A systematic approach for stability-indicating HPLC method optimization for Nilotinib bulk through design of experiment: Application towards characterization of base degradation product by Mass Spectrometry.
Abstract A novel and reliable stability-indicating high-performance liquid chromatography method was developed using design of experiments. Under forced degradation conditions (hydrolysis, oxidative, photolytic and thermal) Nilotinib produced five major degradation products utilizing sodium hydroxide in base hydrolysis. The degradation products were separated by Hypersil ODS column (150 x 4.6 mm i.d., 5 µ) utilizing methanol and 10mM ammonium acetate (pH 3.0, adjusted with acetic acid) as mobile phase in gradient elusion mode at a flow rate of 1.2 mL/min column temperature set at 35°C and UV detection at...
Source: Annales Pharmaceutiques Francaises - November 23, 2020 Category: Drugs & Pharmacology Authors: Narenderan ST, Babu B, Srikanth J, Meyyanathan SN Tags: Ann Pharm Fr Source Type: research

A Drug-Induced Acute Pancreatitis Retrospective Study.
Conclusions: This study has added new evidences about potentially pancreatitis-associated drugs in literature. This is the first study to report definite 5-fluorouracil- and triamcinolone-induced AP. An updated version of the evidence-based literature review is needed to support the clinicians in the identification of the causative drugs. PMID: 33204673 [PubMed - in process] (Source: Canadian Journal of Gastroenterology)
Source: Canadian Journal of Gastroenterology - November 21, 2020 Category: Gastroenterology Tags: Can J Gastroenterol Hepatol Source Type: research

Dasatinib associated lymphadenopathy in a chronic myeloid leukemia patient: A case report
We describe the spectrum of lesions associated with DAL and identify common features with drug-induced lymphadenopathy. (Source: Medicine)
Source: Medicine - November 6, 2020 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Development and validation of a sensitive liquid chromatography tandem mass spectrometry assay for the simultaneous determination of ten kinase inhibitors in human serum and plasma.
Abstract A liquid chromatography tandem mass spectrometry method for the analysis of ten kinase inhibitors (afatinib, axitinib, bosutinib, cabozantinib, dabrafenib, lenvatinib, nilotinib, osimertinib, ruxolitinib, and trametinib) in human serum and plasma for the application in daily clinical routine has been developed and validated according to the US Food and Drug Administration and European Medicines Agency validation guidelines for bioanalytical methods. After protein precipitation of plasma samples with acetonitrile, chromatographic separation was performed at ambient temperature using a Waters XBridge® P...
Source: Analytical and Bioanalytical Chemistry - November 6, 2020 Category: Chemistry Authors: Aghai F, Zimmermann S, Kurlbaum M, Jung P, Pelzer T, Klinker H, Isberner N, Scherf-Clavel O Tags: Anal Bioanal Chem Source Type: research

Concomitant Administration of Direct Oral Anticoagulants in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors
ConclusionIn this small case series, the use of DOACs in CML patients seemed feasible. Additional data on long-term outcomes including a larger cohort of CML patients treated with DOACs are, however, needed. (Source: Clinical Drug Investigation)
Source: Clinical Drug Investigation - October 22, 2020 Category: Drugs & Pharmacology Source Type: research

Four-Dimensional Echocardiographic Evaluation of Left Ventricular Systolic Functions in Patients with Chronic Myeloid Leukaemia Receiving Tyrosine Kinase Inhibitors.
Abstract Tyrosine kinase inhibitors (TKIs) are established treatment for haematological malignancies. However, cardiac adverse effects, including the reduction in left ventricular ejection fraction and symptomatic heart failure remain clinical problems. The purpose of this study was to evaluate the left ventricular systolic functions in patients with chronic myeloid leukaemia receiving TKIs. A cross-sectional and observational study was conducted of 37 patients with chronic myeloid leukaemia receiving dasatinib or nilotinib after imatinib failure. Left ventricular systolic functions were evaluated using four-dimen...
Source: Cardiovascular Toxicology - October 17, 2020 Category: Cardiology Authors: Karakulak UN, Aladag E, Hekimsoy V, Sahiner ML, Kaya EB, Ozer N, Aksu S, Demiroglu H, Goker H, Buyukasik Y, Ozcebe O, Sayinalp N, Haznedaroglu IC Tags: Cardiovasc Toxicol Source Type: research

AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor ‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B.
AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B. Oncol Rep. 2020 Nov;44(5):2211-2218 Authors: Takeda T, Tsubaki M, Genno S, Nemoto C, Onishi Y, Yamamoto Y, Imano M, Satou T, Nishida S Abstract Imatinib is the gold standard in the conventional treatment of chronic myeloid leukemia (CML). However, some patients become resistant to imatinib therapy. To overcome this resistance, second‑generation (dasatinib, nilotinib, and bosutinib) and third‑generation (ponatinib) tyrosine kin...
Source: Oncology Reports - October 3, 2020 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Imatinib/nilotinib
(Source: Reactions Weekly)
Source: Reactions Weekly - October 1, 2020 Category: Drugs & Pharmacology Source Type: research

Modulation of oxidative stress/antioxidative defence in human serum treated by four different tyrosine kinase inhibitors
Recent findings implied the significance of reactive oxygen species (ROS) as a part of tyrosine kinase inhibitors (TKIs) pharmacological activity. Evidences also suggested that toxic effects of TKIs were related to ROS production. The results regarding benefits of vitamin E usage alongside with prescribed TKIs therapy are ambiguous. We aimed to examine oxidative stress and antioxidative defense in human serum treated with four different TKIs and their possible interactions with hydrosoluble vitamin E analog (Trolox). An in-vitro experiment with serum pool as a substitute model was performed. Different parameters of oxidati...
Source: Anti-Cancer Drugs - September 18, 2020 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

Nilotinib-induced liver injury: A case report
Introduction: Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase receptor and is used in the management of chronic myelogenous leukemia (CML). Nilotinib therapy at high doses is associated with elevated serum bilirubin levels. If the serum bilirubin level exceeds 3 times the upper limit of normal, the recommendation is to either adjust nilotinib dosage or temporarily discontinue the treatment. However, it is unclear whether hyperbilirubinemia indicates obvious liver histology damage. Patient concerns: A 24-year-old man with confirmed CML was treated with nilotinib therapy and developed hyperbilirubinemi...
Source: Medicine - September 4, 2020 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research

Tyrosine Kinase Inhibitors Play an Antiviral Action in Patients Affected by Chronic Myeloid Leukemia: A Possible Model Supporting Their Use in the Fight Against SARS-CoV-2
In this study, the CML model was used to test if TKIs would sustain or not the viral replication and if they could damage patient immunity. Firstly, the infection and replication rate of torquetenovirus (TTV), whose load is inversely proportional to the host immunological control, have been measured in CML patients receiving nilotinib. A very low percentage of subjects were infected at baseline, and TTV did not replicate or at least showed a low replication rate during the follow-up, with a mean load comparable to the measured one in healthy subjects. Then, after gene expression profiling experiments, we found that several...
Source: Frontiers in Oncology - September 1, 2020 Category: Cancer & Oncology Source Type: research

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV+ and HPV- Squamous Cell Carcinoma
Conclusion: The selective drug treatment options significantly influenced the expression of CD44 and AREG in HPV– and HPV+ tumor cells, constituting the need for personalized treatment options. (Source: Cancer Genomics and Proteomics)
Source: Cancer Genomics and Proteomics - August 27, 2020 Category: Cancer & Oncology Authors: KANSY, B., ADERHOLD, C., HUBER, L., LUDWIG, S., BIRK, R., LAMMERT, A., LANG, S., ROTTER, N., KRAMER, B. Tags: Experimental Studies Source Type: research

Cost-Effectiveness of First-Line Tyrosine Kinase Inhibitor Therapy Initiation Strategies for Chronic Myeloid Leukemia
Overall survival in chronic myeloid leukemia (CML) in chronic phase is not significantly different by treatment with first-line tyrosine kinase inhibitors (TKIs), but emerging evidence reveals differences in costs and safety profiles. We evaluated the 1-year cost-effectiveness of TKI initiation with imatinib, dasatinib, or nilotinib among a hypothetical cohort of incident patients with CML from a US payer's perspective. (Source: Value in Health)
Source: Value in Health - August 6, 2020 Category: International Medicine & Public Health Authors: Joehl T. Nguyen, Ashley L. Cole, Ashley A. Leech, William A. Wood, Stacie B. Dusetzina Source Type: research

Successful ovarian stimulation and pregnancy in an infertile woman with chronic myeloid leukemia
ConclusionCompared with imatinib, nilotinib achieves earlier and deeper MR that allows safe and timely pregnancies in infertile CML women through IVF process, while patients remain in TFR after delivery. (Source: Journal of Assisted Reproduction and Genetics)
Source: Journal of Assisted Reproduction and Genetics - August 5, 2020 Category: Reproduction Medicine Source Type: research

Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination.
Abstract The development of resistance to endocrine therapy of estrogen receptor alpha (ERα)-positive breast cancer is inevitable, necessitating the introduction of alternative treatment strategies. Therefore, the current study was carried out to investigate the in vivo efficacy and tolerability of nilotinib/rosuvastatin novel combination against ERα-positive breast carcinoma. Results showed that treatment of tumor-bearing mice with nilotinib/rosuvastatin exerted a significant antitumor activity. Mechanistically, the combination treatment efficiently inhibited the in vivo ERα protein expression, ...
Source: Toxicology and Applied Pharmacology - August 5, 2020 Category: Toxicology Authors: Goda AE, Elsisi AE, Sokkar SS, Abdelrazik NM Tags: Toxicol Appl Pharmacol Source Type: research

Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking Screening.
CONCLUSION: These promising drugs could inhibit the replication of the virus; hence, we suggest the repurposing of these compounds for thetreatment of COVID-19. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA. However, the assessment of these potential inhibitors as clinical drugs involves further in vivo tests for these drugs. PMID: 32748740 [PubMed - as supplied by publisher] (Source: Combinatorial Chemistry and High Throughput Screening)
Source: Combinatorial Chemistry and High Throughput Screening - July 29, 2020 Category: Chemistry Authors: Chtita S, Belhassan A, Aouidate A, Belaidi S, Bouachrine M, Lakhlifi T Tags: Comb Chem High Throughput Screen Source Type: research

Eruption of squamous cell carcinomas after beginning nilotinib therapy
Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between the long arms of chromosomes 9 and 22 leading to the formation of a constitutively active tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the treatment of choice for patients diagnosed with CML and have many associated side effects including the rarely-reported eruption of squamous cell carcinomas (SCCs). Herein, we report a patient with CML who presented with sudden onset of multiple scaly lesions on his legs and trunk after beginning treatment with nilotinib, a novel TKI. Six biopsies were performed at his initial presentatio...
Source: Dermatology Online Journal - July 29, 2020 Category: Dermatology Source Type: research

[ASAP] Exploring the Impact of Surfactant Type and Digestion: Highly Digestible Surfactants Improve Oral Bioavailability of Nilotinib
Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.0c00305 (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - July 28, 2020 Category: Drugs & Pharmacology Authors: Niklas J. Koehl †, Rene´ Holm‡§, Martin Kuentz?, Vincent Jannin?#, and Brendan T. Griffin*† Source Type: research

Early prediction of subsequent molecular response to nilotinib in patients with chronic myeloid leukemia: Comparison of the quantification of BCR-ABL1 ratios using ABL1 or GUSB control genes
Publication date: Available online 17 July 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Ruth Stuckey, Luis-Felipe Casado, Dolors Colomer, María Teresa Gómez-Casares, Laura Casas, Valentín García-Gutierrez, José Luis Sastre, Ángel Ramírez-Payer, Ferrán Vall-Llovera, María Ángeles Goñi, Blanca Xicoy, Ana Cristina Godoy, Javier Núñez, Itxaso Mora, Rolando Vallansot, José Luis López-Lorenzo, Luis Palomera, Venancio Conesa, María Soledad Noya, Fermín Sánchez-Guijo (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - July 18, 2020 Category: Pathology Source Type: research

Early prediction of subsequent molecular response to nilotinib in patients with chronic myeloid leukemia: Comparison of the quantification of BCR-ABL1 ratios using ABL1 or GUSB control genes
The molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). The quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to front-line nilotinib was studied using data from 60 patients with chronic phase CML from the ENEST1st substudy. The impact of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early timepoints as independent variables on subsequent MR was determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses (ROC). (Source: Jo...
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Ruth Stuckey, Luis-Felipe Casado, Dolors Colomer, Mar ía Teresa Gómez-Casares, Laura Casas, Valentín García-Gutierrez, José Luis Sastre, Ángel Ramírez-Payer, Ferrán Vall-Llovera, María Ángeles Goñi, Blanca Xicoy, Ana Cristina Godoy, Javier Nú Tags: Regular Article Source Type: research

Inhibition of ABL1 tyrosine kinase reduces HTLV-1 proviral loads in peripheral blood mononuclear cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis
by Daisuke Kodama, Masakazu Tanaka, Toshio Matsuzaki, Kimiko Izumo, Nobuaki Nakano, Eiji Matsuura, Mineki Saito, Masahiro Nagai, Masahisa Horiuchi, Atae Utsunomiya, Hiroshi Takashima, Ryuji Kubota, Shuji Izumo Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellula r genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP p...
Source: PLoS Neglected Tropical Diseases - July 14, 2020 Category: Tropical Medicine Authors: Daisuke Kodama Source Type: research

Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib.
In conclusion, even treated with nilotinib first line, patients with chronic phase CML expressing BCR-ABL1 e13a2 transcript have a lower rate of deep molecular responses. PMID: 32655840 [PubMed] (Source: Oncotarget)
Source: Oncotarget - July 14, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Nilotinib-Induced Immune-Mediated Liver Injury: Corticosteroid as a Possible Therapeutic Option
Conclusion: Nilotinib can cause immune-mediated liver injury. The use of corticosteroid can be treatment option in immune-mediated liver injury. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - July 9, 2020 Category: Cancer & Oncology Source Type: research

Dasatinib-induced Reversible Demyelinating Peripheral Neuropathy and Successful Conversion to Nilotinib in Chronic Myelogenous Leukemia: A Case Report.
Authors: Inoue H, Taji H, Yamada K, Iriyama C, Saito T, Kato H, Yanada M, Yamamoto K, Matsukawa N Abstract Dasatinib, a tyrosine kinase inhibitor, is commonly used in the treatment of chronic myelogenous leukemia. A rare side effect is peripheral neuropathy. A 54-year-old woman experienced gradually accelerated dysesthesia and hypoesthesia in her extremities, 2 months following treatment with dasatinib. Nerve conduction studies revealed a prolonged conduction velocity with temporal dispersion, indicating demyelinating peripheral neuropathy. After changing dasatinib to nilotinib, both her clinical symptoms and elect...
Source: Internal Medicine - July 3, 2020 Category: Internal Medicine Tags: Intern Med Source Type: research

The Risk of Arterial Thrombosis in Patients With Chronic Myeloid Leukemia Treated With Second and Third Generation BCR-ABL Tyrosine Kinase Inhibitors May Be Explained by Their Impact on Endothelial Cells: An In-Vitro Study
This study highlights the endothelial toxicity of ponatinib and provides insights about the mechanisms by which it affects endothelial cell viability. Ponatinib induced apoptosis and necrosis of HUVECs after 72 h. Dasatinib affected endothelial cells in vitro by inhibiting their proliferation and decreased wound closure as soon as 24 h of treatment and even at infra-therapeutic dose (0.005 µM). Comparatively, imatinib, nilotinib, and bosutinib had little impact on endothelial cells at therapeutic concentrations. They did not induce apoptosis nor necrosis, even after 72 h of treatment but they inhibited...
Source: Frontiers in Pharmacology - July 2, 2020 Category: Drugs & Pharmacology Source Type: research

KIT and Melanoma: Biological Insights and Clinical Implications.
Abstract Melanoma, originating from epidermal melanocytes, is a heterogeneous disease that has the highest mortality rate among all types of skin cancers. Numerous studies have revealed the cause of this cancer as related to various somatic driver mutations, including alterations in KIT-a proto-oncogene encoding for a transmembrane receptor tyrosine kinase. Although accounting for only 3% of all melanomas, mutations in c-KIT are mostly derived from acral, mucosal, and chronically sun-damaged melanomas. As an important factor for cell differentiation, proliferation, and survival, inhibition of c-KIT has been exploi...
Source: Yonsei Medical Journal - June 30, 2020 Category: Universities & Medical Training Authors: Pham DDM, Guhan S, Tsao H Tags: Yonsei Med J Source Type: research

Dopamine Metabolite Biomarkers and Testing for Disease Modification in Parkinson Disease —Reply
In Reply LeWitt correctly describes homovanillic acid (HVA) as an unreliable biomarker of Parkinson disease (PD) progression, but our study distinctively evaluated dopamine metabolism in response to nilotinib rather than a biomarker of PD progression, and participants were not taking monoamine oxidase B inhibitors. The hypothesis of this phase 2 study that nilotinib is a disease-modifying drug is based on previous animal data and explored a mix of biomarkers that included dopamine metabolism, α synuclein, and tau proteins. Methodologically, physiologically based population pharmacokinetics/pharmacodynamics studies sh...
Source: JAMA Neurology - June 29, 2020 Category: Neurology Source Type: research

Dopamine Metabolite Biomarkers and Testing for Disease Modification in Parkinson Disease
To the Editor In their randomized, placebo-controlled clinical trial of nilotinib in patients with Parkinson disease (PD), Pagan and colleagues reported dopamine metabolite data as “exploratory biomarkers.” They describe these biochemical findings as providing support for studying nilotinib as a potential disease-modifying therapy. The reasons for their conclusions are largely based on changes in cerebrospinal fluid (CSF) homovanillic acid (HVA) and 3,4-dihydroxyphenylacet ic acid (DOPAC) concentrations (which, from my understanding of the data in Figure 2 A and B in the article, suggest that outlier effects mi...
Source: JAMA Neurology - June 29, 2020 Category: Neurology Source Type: research

Tyrosine Kinase Inhibitors and the Relationship With Adherence, Costs, and Health Care Utilization in Commercially Insured Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Retrospective Claims-Based Study
Objective: To examine the association among tyrosine kinase inhibitor (TKI) out-of-pocket costs, adherence, and health care costs and utilization in a large group of commercially insured patients with chronic myeloid leukemia (CML). Materials and Methods: Patients with CML aged 18 to 64 years were identified using IBM MarketScan Commercial Database between April 1, 2011 and December 31, 2014. Patients were required to be continuously enrolled 3 months before and 12 months after TKI (imatinib, dasatinib, or nilotinib) initiation. TKI adherence is estimated using the proportion of days covered (PDC), defined as the perc...
Source: American Journal of Clinical Oncology - June 26, 2020 Category: Cancer & Oncology Tags: Original Articles: Hematopoietic Source Type: research

Isolated pulmonary vasculitis associated with nilotinib use: A case report
Publication date: Available online 18 June 2020Source: Leukemia Research ReportsAuthor(s): Nicolette T. Morris, Mihaela B. Taylor, Melkon Hacobian, Olga M. Olevsky, Tanaz A. Kermani (Source: Leukemia Research Reports)
Source: Leukemia Research Reports - June 19, 2020 Category: Hematology Source Type: research

Pathological findings suggesting vascular endothelial damage in multiple organs in chronic myelogenous leukemia patients on long-term tyrosine kinase inhibitor therapy.
Abstract A 66-year-old man with hypertension was diagnosed with chronic myelogenous leukemia in 1996. Treatment was started with hydroxycarbamide and imatinib 400 mg in 1996 + 6, which was increased to 600 mg. Although he achieved a complete cytogenic response in 1996 + 9, he could not continue imatinib because of edema; the regimen was changed to nilotinib 800 mg in 1996 + 13. After he achieved a molecular response better than 4.5 in 1996 + 19, he was referred to our hospital. His urinalysis had shown urine protein since 1996 + 1...
Source: International Journal of Hematology - June 17, 2020 Category: Hematology Authors: Seki Y, Nagano O, Koda R, Morita S, Hasegawa G Tags: Int J Hematol Source Type: research

A  multicenter retrospective evaluation of Chronic Myeloid Leukemia (CML) therapy in Austria assessing the impact of early treatment response on patient outcomes in a real-life setting : R-EFECT study.
CONCLUSION: The data are in line with randomized trials demonstrating that ETR is associated with improved survival and thus confirmed these results in patients treated in daily clinical routine. PMID: 32533444 [PubMed - as supplied by publisher] (Source: Wiener Klinische Wochenschrift)
Source: Wiener Klinische Wochenschrift - June 11, 2020 Category: General Medicine Authors: Petzer AL, Sperr WR, Buxhofer-Ausch V, Sliwa T, Schmidt S, Greil R, Wölfler A, Pichler P, Dormann C, Burgstaller S, Tinchon C, Lang A, Goebel F, Uthman S, Muenchmeier N, Valent P Tags: Wien Klin Wochenschr Source Type: research

Adherence to tyrosine kinase inhibitors among adult chronic myeloid leukemia patients in a Malaysia hospital
Conclusion The patients in this study demonstrated a relatively deep molecular response and optimal adherence. Nevertheless, one fourth of them were noncompliant with imatinib. Therefore, active interventions are warranted to prevent treatment-associated adverse events and improve adherence. (Source: International Journal of Clinical Pharmacy)
Source: International Journal of Clinical Pharmacy - June 10, 2020 Category: Drugs & Pharmacology Source Type: research

Chase Dosing of Lipid Formulations to Enhance Oral Bioavailability of Nilotinib in Rats
ConclusionChase dosed LBF enhanced thein vivo bioavailability of nilotinib. Long chain lipids showed superior performance compared to medium chain lipids. Chase dosing appeared to prolong the absorption phase of the drug. Therefore, chase dosing of LBF is favourable compared to lipid suspensions for ‘brick dust’ molecules such as nilotinib.Graphical AbstractThe potential of bio-enabling lipid vehicles, administered via chase dosing and lipid suspensions, has been evaluated as an approach to enhance oral bioavailability of nilotinib. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - June 9, 2020 Category: Drugs & Pharmacology Source Type: research

Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia
The treatment of chronic myeloid leukemia (CML) has been radically changed by the approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity. CML is now managed as a chronic disease requiring long-term treatment and close molecular monitoring. It has been shown that in a substantial number of patients who have achieved a stable deep molecular response (DMR), TKI treatment can be safely discontinued without loss of response. Therefore, treatment-free remission (TFR), through the achievement of a DMR, is increasingly regarded as a feasible treatment goal in many CML patients. However, only nilotinib...
Source: Frontiers in Oncology - June 1, 2020 Category: Cancer & Oncology Source Type: research

Response and Adherence to Nilotinib in Daily practice (RAND study): an in-depth observational study of chronic myeloid leukemia patients treated with nilotinib
AbstractIntroductionThis comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (Cmin) and treatment outcomes.MethodsChronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). NilotinibCmin and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months.ResultsSixty-eight patients (57.5 ± 15.0 years, 49% female) partic...
Source: European Journal of Clinical Pharmacology - June 1, 2020 Category: Drugs & Pharmacology Source Type: research

Leukostasis retinopathy with leukemic infiltrates as onset manifestation of chronic myeloid leukemia: a case report.
CONCLUSION: In our case, the CML-related retinopathy represented the onset sign of the underlying systemic pathology, leading to proper management and treatment, with hematological normalization and resolution of the retinopathy. PMID: 32476461 [PubMed - as supplied by publisher] (Source: European Journal of Ophthalmology)
Source: European Journal of Ophthalmology - May 30, 2020 Category: Opthalmology Authors: Vicini G, Nicolosi C, Malandrino D, Tozzetti C, Rizzo S, Sodi A Tags: Eur J Ophthalmol Source Type: research

Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib
The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total ...
Source: International Journal of Cardiology - May 26, 2020 Category: Cardiology Authors: Anand Prakash Singh, Prachi Umbarkar, Sultan Tousif, Hind Lal Source Type: research

GSE132666 Inhibition of ABL1 tyrosine kinase reduces HTLV-1 in peripheral blood mononuclear cells from HTLV-1-associated myelopathy/tropical spastic paraparesis patients
Contributors : Daisuke Kodama ; Masakazu Tanaka ; Toshio Matsuzaki ; Kimiko Izumo ; Nobuaki Nakano ; Eiji Matsuura ; Mineki Saito ; Masahiro Nagai ; Masahisa Horinouchi ; Atae Utsunomiya ; Hiroshi Takashima ; Ryuji Kubota ; Shuji IzumoSeries Type : Expression profiling by arrayOrganism : Homo sapiensHuman T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles played by cellular genes in HTLV-1-infect...
Source: GEO: Gene Expression Omnibus - May 26, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Myeloid diseases —Chronic Myeloid Leukemia (CML)—report from ASH 2019 on new developments
SummaryThe recent American Society of Hematology (ASH) annual meeting, held in Orlando, Florida, in December 2019 was an exciting meeting for researchers and clinicians working in the field of chronic myeloid leukemia (CML), as well as for patients suffering from the disease. Interesting updates were presented on new kinase inhibitors (TKI) demonstrating great potential with low toxicities in heavily pretreated patients. Moreover, the 10-year follow-up data of the ENESTnd Study, comparing 2nd generation (2ndG) TKI nilotinib with imatinib showed a  continuous benefit of the 2ndG TKI in achieving deeper molecular respon...
Source: Memo - Magazine of European Medical Oncology - May 25, 2020 Category: Cancer & Oncology Source Type: research

Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro
We investigated possible conditions or drugs that could target P-glycoprotein (P-gp)-overexpressing drug-resistant KBV20C cancer cells. Specifically, we focused on identifying a single treatment with a relatively low half maximal inhibitory concentration (IC50). Our approach utilized repurposing drugs, which are already used in clinical practice. We evaluated 13 TKIs (gefitinib, imatinib, erlotinib, nilotinib, pazopanib, masatinib, sunitinib, sorafenib, regorafenib, lapatinib, vandetanib, cediranib, and crizotinib) for their sensitizing effects on P-gp-overexpressing drug-resistant KBV20C cells. We found that crizotinib ha...
Source: Frontiers in Oncology - May 11, 2020 Category: Cancer & Oncology Source Type: research

BCR ‐ABL Tyrosine Kinase Inhibitors Promote Pathological Changes in Dilator Phenotype in the Human Microvasculature
ConclusionIncubating human arterioles with imatinib or nilotinib switches the mediator of FMD from vasoprotective nitric oxide to pro ‐inflammatory H2O2. (Source: Microcirculation)
Source: Microcirculation - May 11, 2020 Category: Research Authors: Matthew J. Durand, Shelby N. Hader, Alexa Derayunan, Natalya Zinkevich, Jennifer J. McIntosh, Andreas M. Beyer Tags: ORIGINAL RESEARCH Source Type: research

A stability indicating method development and validation for separation of process related impurities and characterization of unknown impurities of tyrosine kinase inhibitor Nilotinib by RP-HPLC, NMR spectroscopy and ESI-MS
Publication date: Available online 4 May 2020Source: Materials Today: ProceedingsAuthor(s): Ramana Reddy Gopireddy, Arthanareeswari Maruthapillai (Source: Materials Today: Proceedings)
Source: Materials Today: Proceedings - May 5, 2020 Category: Materials Science Source Type: research