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Id: biblio-837937
Autor: Leitão, Juliana Ribeiro; Valente, Neusa Yuriko Sakai; Kakizaki, Priscila; Veronez, Isis Suga; Pires, Mario Cezar.
Título: Lichen planopilaris-like eruption during treatment with tyrosine kinase inhibitor nilotinib
Fonte: An. bras. dermatol;91(5,supl.1):45-47, Sept.-Oct. 2016. graf.
Idioma: en.
Resumo: Abstract Tyrosine kinase inhibitors are effective as a target therapy for malignant neoplasms. Imatinib was the first tyrosine kinase inhibitor used. After its introduction, several other drugs have appeared with a similar mechanism of action, but less prone to causing resistance. Even though these drugs are selective, their toxicity does not exclusively target cancer cells, and skin toxicity is the most common non-hematologic adverse effect. We report an eruption similar to lichen planopilaris that developed during therapy with nilotinib, a second generation tyrosine kinase inhibitor, in a patient with chronic myeloid leukemia resistant to imatinib. In a literature review, we found only one report of non-scarring alopecia due to the use of nilotinib.
Descritores: Pirimidinas/efeitos adversos
Erupção por Droga/etiologia
Erupção por Droga/patologia
Inibidores de Proteínas Quinases/efeitos adversos
Líquen Plano/patologia
-Biópsia
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Alopecia/induzido quimicamente
Alopecia/patologia
Mesilato de Imatinib/efeitos adversos
Antineoplásicos/efeitos adversos
Limites: Humanos
Feminino
Pessoa de Meia-Idade
Tipo de Publ: Relatos de Casos
Responsável: BR1.1 - BIREME


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Id: lil-582750
Autor: Simões, Belinda Pinto; Braga Junior, José Wilson Ramos; Rego, Maria Aparecida do Carmo; Souza, Cármino Antônio de.
Título: Importance of monitoring and early switch to second generation tyrosine kinase inhibitors for the prognosis of patients with chronic myeloid leukemia with imatinib resistance or intolerance
Fonte: Rev. bras. hematol. hemoter;33(1):65-72, Feb. 2011. tab.
Idioma: en.
Resumo: Imatinib mesylate was the first BCR-ABL-target agent approved for the treatment of chronic myeloid leukemia. Although most patients respond well to imatinib therapy, the literature shows that one third develops resistance or intolerance. The timing of second-line treatment after failure of initial treatment may have a significant impact on long-term outcome. Thus, appropriate monitoring to identify resistance and/or intolerance is crucial to early intervention with second generation tyrosine kinase inhibitors and attainment of better results.
Descritores: Prognóstico
Pirimidinas/uso terapêutico
Resistência a Medicamentos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Monitoramento de Medicamentos
Receptores Proteína Tirosina Quinases
Resistencia a Medicamentos Antineoplásicos
Monitoramento
Mesilato de Imatinib
Antineoplásicos/administração & dosagem
Limites: Humanos
Tipo de Publ: Revisão
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: lil-601010
Autor: Martins, Darlize Hübner; Wagner, Sandrine Comparsi; Santos, Tamyris Vianna dos; Lizot, Lilian de Lima Feltraco; Antunes, Marina Venzon; Capra, Marcelo; Linden, Rafael.
Título: Monitoring imatinib plasma concentrations in chronic myeloid leukemia
Fonte: Rev. bras. hematol. hemoter;33(4):302-306, 2011.
Idioma: en.
Resumo: Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug.
Descritores: Plasma
Pirimidinas/farmacocinética
Algoritmos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Cromatografia
Monitoramento de Medicamentos
Tratamento Farmacológico
Citocromo P-450 CYP3A/metabolismo
Mesilato de Imatinib
/farmacocinética
FRUCTANSTEMEFOS/farmacocinética
Antineoplásicos/uso terapêutico
Tipo de Publ: Revisão
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: lil-601001
Autor: Wallemacq, Pierre.
Título: Therapeutic drug monitoring of imatinib
Fonte: Rev. bras. hematol. hemoter;33(4):257-258, 2011.
Idioma: en.
Descritores: Monitoramento de Medicamentos
Mesilato de Imatinib
Tipo de Publ: Comentário
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-951935
Autor: Al-Rasheed, Nawal Mohammed; El-Masry, Thanaa Ahmed; Tousson, Ehab; Hassan, Hanan Mohammad; Al-Ghadeer, Areej.
Título: Hepatic protective effect of grape seed proanthocyanidin extract against Gleevec-induced apoptosis, liver Injury and Ki67 alterations in rats
Fonte: Braz. J. Pharm. Sci. (Online);54(2):e17391, 2018. tab, graf.
Idioma: en.
Resumo: ABSTRACT Gleevec (imatinib) is an antineoplastic chemotherapeutic agent used in the treatment of many types of cancer. The current study was conducted to examine the possible modifying effects of grape seeds proanthocyandins extract (GSPE) against apoptosis, liver injury and Ki67 alterations induced by Gleevec in male rats. 40 male albino rats were equally divided into four groups (First and second groups were control and GSPE groups; third group was Gleevec group and fourth group was treated with Gleevec and GSPE). Gleevec induced elevations in P53 and depletion of Bcl2 levels in liver tissues were compared with the control group. Liver sections in rats treated with Gleevec exhibited marked cellular infiltrations, vacuolar degeneration hepatocytes, numerous apoptotic cells, and congestion in central and portal veins, as well as a significant increase in the proliferating of Ki67 after Gleevec injection as compared with control group. In contrast, treatment with Gleevec and GSPE showed a moderate to good degree of improvement in hepatocytes with a significant increase in Ki67, a decrease in P53 and an increase in Bcl2 levels in liver tissues compared to treatment with Gleevec. Therefore, Gleevec induces apoptosis, injury and Ki67 changes in rat liver, whereas GSPE modulates these alternations.
Descritores: Proantocianidinas/efeitos adversos
Extrato de Sementes de Uva/uso terapêutico
-Apoptose
Antígeno Ki-67/farmacologia
Mesilato de Imatinib/efeitos adversos
Fígado
Limites: Ratos
Responsável: BR1.1 - BIREME


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Id: biblio-959393
Autor: Navarrete M, Andrés; Momblán G, Dulce; Ibarzaval O, Ainitze; Corcelles C, Ricard; Jiménez-Toscano, Marta; Lacy F, Antonio.
Título: Modificación del abordaje quirúrgico en tumores estromales gástricos posterior a neoadyuvancia con Imatinib / Change of surgical approach in gastrointestinal stromal tumors after neoadyuvant therapy with Imatinib
Fonte: Rev. chil. cir;70(4):342-349, ago. 2018. tab, ilus.
Idioma: es.
Resumo: Resumen Introducción: El tratamiento de los tumores estromales gastrointestinales (GIST) de alto riesgo es quirúrgico. Su resultado podría variar al usarse neoadyuvancia. Objetivo: Evaluar si el uso de la terapia neoadyuvante con imatinib puede cambiar el abordaje quirúrgico en los tumores estromales gastrointestinales de alto riesgo. Materiales y Métodos: Se realizó un análisis retrospectivo en el Hospital Clínic de Barcelona entre enero de 2002 y mayo de 2016. Resultados: Se obtuvo un total de 8 pacientes. La edad media fue 66,1 ± 13,3 años. La ubicación del tumor fue de 37,5% (3) en el tercio superior, el 50% (4) en el tercio medio y el 12,5% (1) en el tercio inferior. Debido a la clasificación de riesgo alto, la ubicación y/o la necesidad de resecciones multiviscerales, se indicó, previa evaluación comité oncológico, realizar terapia neoadyuvante. La mediana de tiempo de neoadyuvancia fue de 30 semanas. En el 100% (8) de los casos se logró un cambio de enfoque quirúrgico después de la utilización de imatinib. En todos los casos se realizó un resección local (7 laparoscópica y 1 endolaparoscópica) con márgenes negativos La biopsia posoperatoria mostró un promedio de 51,2% de reducción del tamaño tumoral inicial, lo que resultó en una diferencia estadística (p < 0,01) con el tamaño inicial de las lesiones. Durante el seguimiento, tanto la sobrevida relacionada al tumor como la global, fue de un 100%. Conclusión: La terapia neoadyuvante podría cambiar el abordaje quirúrgico de los pacientes con GIST gástrico de riesgo intermedio o alto mediante la reducción del tamaño tumoral, permitiendo realizar cirugías más económicas y logrando resultados oncológicos adecuados.

Introduction: The treatment of high-risk gastrointestinal stromal tumors (GIST) is surgical. Results may change when using neoadjuvant. Objetive: To evaluated if the use of neoadjuvant therapy with imatinib can change the surgical approach in high risk gastrointestinal stromal tumors (GIST). Materials and Methods: A retrospective analysis was performed from a prospective collected database in Hospital Clinic of Barcelona between January 2002 and May 2016. Results: A total of 8 patients were analyzed with a mean age of 66.1 ± 13.3 years. The tumor location was upper third 37.5% (3) cases, 50% (4) in the middle third and 12.5% (1) in lower third. Because of high risk classification, location and the need of multivisceral resections, neoadjuvant therapy was indicated. The median time of neoadjuvant therapy was 30 weeks. In 87.5% (7) cases a change of surgical approach was achieved after the use of imatinib. In 100% of our series laparoscopic wedge resection was performed achieving negative margins of resection. The postoperative biopsy showed 51.2% of reduction of initial tumor size, resulting in statistical difference (p < 0.01). All patients are alive and 100% of tumor related survival was achieved. Conclusion: Neoadjuvant therapy maybe can change the surgical approach of patients with high-intermediate risk gastric GIST by reducing tumor size. This response also eventually can achieve optimal oncological outcome.
Descritores: Neoplasias Gástricas/tratamento farmacológico
Terapia Neoadjuvante/métodos
Tumores do Estroma Gastrointestinal/tratamento farmacológico
Mesilato de Imatinib/uso terapêutico
Antineoplásicos/uso terapêutico
-Neoplasias Gástricas/cirurgia
Estudos Retrospectivos
Resultado do Tratamento
Laparoscopia
Tumores do Estroma Gastrointestinal/cirurgia
Limites: Humanos
Masculino
Feminino
Adulto
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Tipo de Publ: Estudo Clínico
Responsável: CL61.1 - Biblioteca Central Campus Sur


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Id: lil-764216
Autor: Furtado, Vanessa Fiorini; Santos, Gustavo Rengel; Carvalho, Denise Siqueira de; Staziaki, Pedro Vinícius; Pasquini, Ricardo; Funke, Vaneuza Araújo Moreira.
Título: Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase
Fonte: Rev. bras. hematol. hemoter;37(5):341-347, Sept.-Oct. 2015. tab, graf.
Idioma: en.
Resumo: BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or <1 × 105/µL and white blood cells > 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin < 10 g/dL, time between diagnosis of chronic myeloid leukemia and imatinib treatment, and hematologic toxicity.RESULTS: Risk factors for poor survival in multivariate analysis were Grades 3-4 hematologic toxicity (p-value = 0.001), blasts 10-29% (p-value = 0.023), and hemoglobin < 10 g/dL (p-value = 0.04). Risk factors for not achieving major cytogenetic response were blasts 10-29% (p-value = 0.007), hemoglobin < 10 g/dL (p-value = 0.001), and previous use of interferon (p-value = 0.032). Risk factors for progression to the blast phase were hemoglobin < 10 g/dL (p-value = 0.005), basophils ≥ 20% (p-value = 0.023), and time from diagnosis of chronic myeloid leukemia to imatinib treatment > 12 months (p-value = 0.030).CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.
Descritores: Prognóstico
Leucemia Mieloide de Fase Acelerada
Leucemia Mielogênica Crônica BCR-ABL Positiva
Mortalidade
Mesilato de Imatinib
Limites: Humanos
Masculino
Feminino
Criança
Adolescente
Adulto
Pessoa de Meia-Idade
Idoso
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-898930
Autor: Vieira-Mion, Ana Lucia; Pereira, Noemi Farah; Funke, Vaneuza Araujo Moreira; Pasquini, Ricardo.
Título: Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia
Fonte: Rev. bras. hematol. hemoter;39(3):210-215, July-Sept. 2017. tab, graf.
Idioma: en.
Resumo: Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1 IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1 IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1 IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.
Descritores: Brasil
Leucemia Mielogênica Crônica BCR-ABL Positiva
Mesilato de Imatinib
-Proteínas Tirosina Quinases
Proteínas de Fusão bcr-abl
Reação em Cadeia da Polimerase em Tempo Real
Limites: Humanos
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-898946
Autor: Kumar, Rajiv; Kapoor, Rajan.
Título: Primary imatinib failure rescued by dasatinib and maintained by reintroduction of imatinib
Fonte: Rev. bras. hematol. hemoter;39(4):360-363, Oct.-Dec. 2017. graf.
Idioma: en.
Descritores: Proteínas Tirosina Quinases
Leucemia Mielogênica Crônica BCR-ABL Positiva
Mesilato de Imatinib
Limites: Humanos
Masculino
Idoso
Tipo de Publ: Relatos de Casos
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-1008520
Autor: Prado, Fernando Kaneko.
Título: Development of analytical method for quantification of antineoplastic in drug delivery systems.
Fonte: São Paulo; s.n; 2019. 59 p. graf, tab, ilus.
Idioma: pt.
Tese: Apresentada a Universidade de São Paulo.Faculdade de Ciências Farmacêuticas para obtenção do grau de Mestre.
Resumo: Nos últimos anos têm crescido cada vez mais o número de pesquisas envolvendo nanotecnologia para obtenção de medicamentos com liberação controlada, pois esses sistemas podem: proteger o fármaco de incompatibilidades tanto biológicas quanto físico-químicas assim como controlar a biodisponibilidade do fármaco. Embora com todas essas vantagens não existem métodos in vitro realmente capazes de prever com precisão a liberação dos fármacos por esses sistemas, por esse motivo, é muito importante o desenvolvimento de métodos de liberação in vitro para determinar a cinética de liberação desses sistemas.O presente trabalho teve como objetivo desenvolver e validar os métodos de eletroforese capilar (CE) e cromatografia líquida de alta eficiência (HPLC) para determinar a eficiência de encapsulação do fármaco imatinibe em nanopartículaspreviamente elaboradas e caracterizadas, assim como estudar sua liberação in vitro por CE. As nanopartículas foramdesenvolvidas pelo método de nanoprecipitaçãoe caracterizadas quanto ao tamanho, potencial zeta, morfologia e eficiência de encapsulação. A eletroforese capilar é uma técnica alternativa muito promissora em relação ao HPLC devido ao seu baixo custo, menor tempo de corrida e menos poluente ao meio ambiente. Os métodos de quantificação por CE e HPLCforam desenvolvidose validadossegundo as diretrizes do ICH, Farmacopeia Americana e ANVISA, permitindo desenvolver um estudo de liberação.As nanoesferas desenvolvidas apresentaram diâmetro médio próximo a 150nm, com índice de polidispersão menor que 0,1 e aproximadamente 90% de eficiência de encapsulação. Ambos métodos se mostraram lineares com coeficientes de determinação superiores a 0,99, os métodos se mostraram precisos (%DPR< 2), exatos(101,0±4,2% e 98,0±2,5% para HPLC e CE, respectivamente)e seletivos.O método de CE permitiu desenvolver um método de estudo de liberação independente das membranas de diálise

In recent years, there has been a growing number of researches involving nanotechnology to obtain controlled release drugs, these systems can: protect the drug against biological and physico-chemical incompatibilities; controlling the bioavailability of the drug. Although with all these advantages there are no in vitro methods really capable of accurately predicting drugs release by such systems, therefore, the development of in vitro release methods to determine the release kinetics of such systems is very important. The objective of the present work was to develop and validate capillary electrophoresis (CE) and HPLC methods to determine the encapsulation efficiency of the imatinib drug in previously elaborated and characterized nanoparticles, as well as to study its release in vitro by CE method. The nanoparticles were synthesized using the nanoprecipitation method and characterized by size, zeta potential, morphology and encapsulation efficiency. Capillary electrophoresis is a very promising alternative to HPLC because of its low cost, less runtime and less polluting environment. The CE and HPLC methodswere developed and validated according ICH, American Pharmacopoeia and ANVISA guidelines.Developed nanospheres had an average diameter close to 150nm, with polydispersity index less than 0.1 and approximately 90% encapsulation efficiency. Both methods were linear with determination coefficients higher than 0.99, the methods were precise (%RSD < 2), accurate (101.0±4,2% and 98.0±2,5% for HPLC and CE, respectively) and selective. Capillary electrophoresis method allowed to develop a drug release study independent of dialysis membranes
Descritores: Nanopartículas
Liberação Controlada de Fármacos
-Técnicas In Vitro
Cromatografia Líquida de Alta Pressão/métodos
Eletroforese Capilar/métodos
Mesilato de Imatinib/análise
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas
BR40.1; T615.19015, P896d. 30100022606-F



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