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1.
Article in Chinese | WPRIM | ID: wpr-880097

ABSTRACT

OBJECTIVE@#To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP).@*METHODS@#Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment.@*RESULTS@#Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABL@*CONCLUSION@#In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , China , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines , Pyrimidines/therapeutic use , Treatment Outcome
2.
An. bras. dermatol ; 95(4): 473-476, July-Aug. 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1130913

ABSTRACT

Abstract Vitiligo is a disease that causes macules and achromic and/or hypochromic patches, which can affect from small areas to the entire tegument. Treatment options are few and are generally ineffective. Recently, some case reports have appeared which show positive results with the use of Janus kinase inhibitors associated with phototherapy. This report details the case of a patient with rheumatoid arthritis associated with vitiligo in treatment for two years, whose condition partially improved initially after eight months of oral tofacitinib at a dose of 5 mg twice a day, without exposure to ultraviolet radiation and with continuous improvement during these two years of treatment.


Subject(s)
Humans , Male , Female , Adult , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Ultraviolet Therapy , Vitiligo/drug therapy , Ultraviolet Rays , Treatment Outcome
3.
Rev. méd. Chile ; 148(7): 1039-1043, jul. 2020. graf
Article in Spanish | LILACS | ID: biblio-1139408

ABSTRACT

Biological therapy dramatically changed the management of Ulcerative Colitis (UC). However, a significant number of these patients fail to respond or have secondary loss of response to this strategy. In this clinical situation, the options include intensification of anti-TNF therapy, the use of a second anti-TNF or being switched to another drug class. Among the later, tofacitinib, an oral small molecule directed against the JAK/STAT pathway, is safe and effective in inducing and maintaining remission in patients with moderate-severe UC. We report two patients with UC refractory to conventional treatment and biological therapy, who responded successfully to the use of tofacitinib.


Subject(s)
Humans , Male , Middle Aged , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Colitis, Ulcerative/drug therapy , Protein Kinase Inhibitors/therapeutic use , Colitis, Ulcerative/diagnostic imaging , Colonoscopy , Treatment Outcome
4.
Arq. gastroenterol ; 55(2): 198-200, Apr.-June 2018. graf
Article in English | LILACS | ID: biblio-1038706

ABSTRACT

ABSTRACT Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.


RESUMO Os inibidores das Janus kinases (JAK) têm sido incorporados ao tratamento de doenças imunomediadas, como artrite reumatoide e, além disso, têm sido testados no tratamento da psoríase e doenças inflamatórias intestinais, tanto na retocolite ulcerativa quanto na doença de Crohn. Tofacitinibe é uma droga do grupo das pequenas moléculas de uso oral que inibe as Janus kinases 1 e 3 e, em menor grau, a Janus kinases 2. Esta inibição promove o bloqueio de uma série de citocinas pró-inflamatórias que estão envolvidas na patogênese das doenças inflamatórias intestinais e desempenham importante papel nos processos imunes, tais como ativação, função e proliferação linfocitária. Nesta presente comunicação, relatamos um caso de um paciente portador de retocolite ulcerativa refratária a três agentes biológicos (infliximabe, adalimumabe e vedolizumabe), com diferentes mecanismos de ação, que recusou o tratamento cirúrgico, porém, apresentou boa resposta com o uso de tofacitinibe, com remissão clínica e endoscópica. Não foram evidenciados efeitos colaterais com a droga. O presente caso ilustra as dificuldades que podemos enfrentar em relação à identificação da expressão do correto mecanismo de ação envolvido na patogênese dos pacientes com retocolite ulcerativa e a importância de um novo agente terapêutico com diferente mecanismo de ação, como o tofacitinibe.


Subject(s)
Humans , Male , Adult , Piperidines/therapeutic use , Colitis, Ulcerative/drug therapy , Integrins/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Integrins/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Infliximab/therapeutic use
6.
Rev. chil. dermatol ; 32(3): 159-161, 2016. ilus
Article in Spanish | LILACS | ID: biblio-947767

ABSTRACT

Nilotinib es un inhibidor altamente selectivo de BCR-ABL tirosina kinasa usado para el tratamiento de Leucemia mieloide crónica. Las reacciones cutáneas fueron uno de los efectos adversos no hematológicos más frecuentemente reportados en relación al uso de esta droga. El presente artículo documenta el caso una paciente femenina de 17 años de edad diagnosticada con Leucemia mieloide crónica que había estado en tratamiento con Nilotinib por 5 meses desarrollando una reacción tipo queratosis pilar. La paciente fue tratada con medidas generales, Urea 15% y antihistamínicos, con cese del prurito. Es importante reconocer las reacciones cutáneas asociadas al uso de Nilotinib para así otorgar alivio oportuno de los síntomas con el fin de lograr una mejor adherencia al tratamiento de la Leucemia mieloide crónica y mejorar la calidad de vida del paciente.


Nilotinib is a highly selective inhibitor of BCR-ABL tyrosine kinase. It is used as a treatment for chronic myelogenous leukemia (CML). Cutaneous reactions are one of the most common non-hematologic reported adverse effects. The present article documents the case of a 17-year-old female patient diagnosed with CML. She was treated with nilotinib for 5 months and developed a keratosis pilaris-like reaction. The patient was treated with general measures, topical 15%-urea and antihistamines with improvement and cessation of pruritus. It is imperative to recognize the cutaneous adverse effects associated with the use of new oncologic treatments such as nilotinib.


Subject(s)
Humans , Female , Adolescent , Pyrimidines/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Keratosis/chemically induced , Pyrimidines/therapeutic use , Drug Eruptions
7.
Rev. bras. reumatol ; 55(6): 512-521, nov.-dez. 2015. graf
Article in English | LILACS | ID: lil-770015

ABSTRACT

Resumo Em 2014, o tofacitinibe, um medicamento modificador do curso da doença (MMCD) sintético, alvo-específico, inibidor seletivo das Janus quinases (JAK), foi aprovado para uso no Brasil. Este documento de posicionamento tem o objetivo de atualizar as recomendações da Sociedade Brasileira de Reumatologia (SBR) sobre o tratamento da artrite reumatoide (AR) no Brasil, especificamente com relação ao uso de MMCD sintéticos alvo-específicos. O método dessa recomendação incluiu revisão bibliográfica de artigos científicos, feita na base de dados Medline. Após a revisão, foi produzido um texto, que responde a perguntas na estrutura Pico, e considera questões de eficácia e segurança do uso do tofacitinibe para tratamento de AR em diferentes situações (como primeira linha de tratamento, após falha ao metotrexato [MTX] ou outros MMCD sintéticos convencionais, após falha da terapia biológica). Com base nas evidências existentes, e considerando os dados disponíveis sobre eficácia, segurança e custo das medicações disponíveis para tratamento da doença no Brasil, a Comissão de AR da SBR, após processo de discussão e votação de propostas, estabeleceu o seguinte posicionamento sobre o uso de tofacitinibe para o tratamento da AR no Brasil: “Tofacitinibe, em monoterapia ou em associação ao MTX, é uma opção para os pacientes com AR em atividade moderada ou alta, após falha de pelo menos dois esquemas com diferentes MMCD sintéticos e um esquema de MMCD biológico”. O grau de concordância com essa recomendação foi 7,5. Esse posicionamento poderá ser revisto nos próximos anos, com a maior experiência adquirida com o uso do medicamento.


Abstract In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: “Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD.” The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication.


Subject(s)
Humans , Piperidines/therapeutic use , Arthritis, Rheumatoid/drug therapy , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Antirheumatic Agents/therapeutic use , Rheumatology , Societies, Medical , Brazil , Methotrexate/therapeutic use , Treatment Failure , Drug Therapy, Combination
8.
Clinics ; 70(8): 550-555, 08/2015. tab, graf
Article in English | LILACS | ID: lil-753967

ABSTRACT

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome ...


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Agents/therapeutic use , Dasatinib/therapeutic use , Drug Resistance/drug effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/therapeutic use , Bone Marrow Examination , Disease-Free Survival , Fusion Proteins, bcr-abl/genetics , Kaplan-Meier Estimate , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Mutation , Real-Time Polymerase Chain Reaction , Time Factors , Treatment Outcome
9.
Rev. bras. ginecol. obstet ; 37(1): 24-29, 01/2015. tab
Article in English | LILACS | ID: lil-732875

ABSTRACT

PURPOSE: To verify the predictors of intravasation rate during hysteroscopy. METHODS: Prospective observational study (Canadian Task Force classification II-1). All cases (n=200 women; 22 to 86 years old) were treated in an operating room setting. Considering respective bag overfill to calculate water balance, we tested two multiple linear regression models: one for total intravasation (mL) and the other for absorption rate (mL.min-1). The predictors tested (independent variables) were energy (mono/bipolar), tube patency (with/without tubal ligation), hysterometry (cm), age≤50 years, body surface area (m2), surgical complexity (with/without myomectomy) and duration (min). RESULTS: Mean intravasation was significantly higher when myomectomy was performed (442±616 versus 223±332 mL; p<0.01). In the proposed multiple linear regression models for total intravasation (adjusted R2=0.44; p<0.01), the only significant predictors were myomectomy and duration (p<0.01).In the proposed model for intravasation rate (R2=0.39; p<0.01), only myomectomy and hysterometry were significant predictors (p=0.02 and p<0.01, respectively). CONCLUSIONS: Not only myomectomy but also hysterometry were significant predictors of intravasation rate during operative hysteroscopy. .


OBJETIVO: Testar preditores do ritmo de intravasamento durante histeroscopia cirúrgica. MÉTODOS: Estudo prospectivo observacional (classificação: Canadian Task Force II-1) incluindo casos conduzidos em centro cirúrgico (n=200 mulheres; 22 a 86 anos de idade). Considerando os erros de aferição nas embalagens de solução de irrigação para calcular o balanço hídrico, nós testamos dois modelos de regressão linear múltipla: um para intravasamento total (mL) e outro para ritmo de intravasamento (mL.min-1). Os preditores testados (variáveis independentes) foram energia (mono/bipolar), permeabilidade tubária (com/sem ligadura tubária), histerometria (cm), status ovariano (idade≤50 anos), área de superfície corporal (m2), complexidade de cirurgia (com/sem miomectomia) e tempo de ressecção (min). RESULTADOS: O intravasamento médio foi significativamente maior quando miomectomia foi realizada (442±616 versus 223±332 mL, p<0,01). No modelo proposto para intravasamento total (R2 ajustado=0,44; p<0,01), os únicos preditores significativos foram miomectomia e tempo de duração (p<0,01). No modelo proposto para a taxa de intravasamento (R2=0,39; p<0,01), somente miomectomia e histerometria foram preditores significativos (p=0,02 e p<0,01, respectivamente). CONCLUSÕES: Não só a miomectomia mas também a histerometria são preditores significativo da taxa de intravasamento durante histeroscopia cirúrgica. .


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Pyrimidines/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Administration, Oral , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Drug Administration Schedule , Pyrimidines/administration & dosage , Pyrimidines/adverse effects
10.
Article in English | WPRIM | ID: wpr-99852

ABSTRACT

Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Animals , Biphenyl Compounds/therapeutic use , Cardiomyopathies/chemically induced , Doxorubicin/toxicity , Echocardiography , Hemodynamics , Pyrimidines/therapeutic use , Rats , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1/chemistry , Survival Rate , Tetrazoles/therapeutic use , Ventricular Function, Left/physiology
11.
Article in English | WPRIM | ID: wpr-166135

ABSTRACT

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.


Subject(s)
3-Iodobenzylguanidine , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Anterior Wall Myocardial Infarction/drug therapy , Biphenyl Compounds/therapeutic use , Cardiotonic Agents/therapeutic use , Disease Models, Animal , Echocardiography , Fluorodeoxyglucose F18 , Perindopril/therapeutic use , Positron-Emission Tomography , Pyrimidines/therapeutic use , Random Allocation , Swine , Tetrazoles/therapeutic use , Tomography, Emission-Computed, Single-Photon , Valsartan/therapeutic use , Ventricular Function, Left/physiology
12.
Gut and Liver ; : 18-27, 2015.
Article in English | WPRIM | ID: wpr-61579

ABSTRACT

Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are being investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are being used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Factors/therapeutic use , Cell Adhesion Molecules/antagonists & inhibitors , Colitis, Ulcerative/drug therapy , Humans , Janus Kinases/antagonists & inhibitors , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use
13.
Clinics ; 69(11): 758-762, 11/2014. tab, graf
Article in English | LILACS | ID: lil-731105

ABSTRACT

OBJECTIVES: Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. METHODS: Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. RESULTS: A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p = 0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. CONCLUSIONS: IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection. .


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Stromal Tumors/drug therapy , Neoplasm Recurrence, Local/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/secondary , Gastrointestinal Stromal Tumors/surgery , Liver Neoplasms/secondary , Neoadjuvant Therapy , Neoplasm Metastasis/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Preoperative Care , Preoperative Period , Reproducibility of Results , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor Burden
14.
Rev. méd. Chile ; 142(4): 516-520, abr. 2014. graf, tab
Article in Spanish | LILACS | ID: lil-716224

ABSTRACT

We report a 58 year-old-man without comorbid conditions, with a history of two months of weight loss, malaise and headache. His initial laboratory analysis showed leukocytosis of 16,100/mL with 65% eosinophils and an absolute eosinophil count of 10,465/mL. Both bone marrow biopsy and aspirate showed infiltration by mature appearing eosinophils. Treatment was started with hydroxyurea, associated with prednisone without satisfactory decrease in the eosinophil count. Polymerase chain reaction showed the presence of the gene fusion product FIP1L1/PDGFRA. Imatinib therapy was initiated, resulting in a rapid and progressive reduction in the absolute eosinophil count, with normalization at the second week of treatment. The incidence of the myeloproliferative variant causing hypereosinophilic syndrome is rare. However, the dramatic response to imatinib emphasizes the need to study the presence of the fusion product FIP1L1/PDGFRA in all patients with eosinophilia of unknown etiology.


Subject(s)
Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Hypereosinophilic Syndrome/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Treatment Outcome
15.
Rev. chil. cir ; 66(2): 175-180, abr. 2014. ilus
Article in Spanish | LILACS | ID: lil-706537

ABSTRACT

Introducción: Los tumores estromales gastrointestinales (GIST) del recto son muy raros. En la última década se ha planteado la neoadyuvancia con imatinib en los casos de tumores localmente avanzados o inicialmente irresecables. Caso clínico: Se presenta una paciente portadora de un GIST maligno del tabique rectovaginal inicialmente considerado irresecable que fue sometido a neoadyuvancia con Imatinib como terapia de inducción durante 3 meses, logrando una respuesta clínica notable que permitió realizar una resección local exitosa por vía endoanal. La presencia de factores pronósticos deletéreos (tamaño tumoral mayor de 5 cm y 13 mitosis por 50 campos de aumento mayor) determinó la mantención del tratamiento con Imatinib por 15 meses luego de la cirugía con el fin de reducir el riesgo de recidiva local. Luego de 20 meses de seguimiento la paciente está libre de enfermedad, con continencia fecal plena, ha recuperado la actividad sexual, aunque persisten algunos efectos residuales de la droga que están en franca disminución. Conclusión: La neoadyuvancia con imatinib se considera actualmente la terapia estándar en el manejo de los GIST localmente avanzados y/o irresecables.


Background: Rectal gastrointestinal stromal tumors (GIST) are rare. Neo-adjuvant therapy with imatinib is recommended for locally advanced or non-resectable tumors. Case report: We report a 63 years old woman with a malignant GIST located in the recto-vaginal septum which was initially considered non-resectable. The patient was treated with imatinib as induction therapy for three months. After this lapse the tumor was successfully excised using an endo-anal approach. Due to a tumor size over 5 cm and the presence of 13 mitoses per 50 high power fields, two bad prognostic factors, treatment with imatinib was maintained for 15 months after surgery. After 20 months of follow up, the patient is free of disease with complete fecal continence and with an adequate sexual life. Secondary effects of imatinib are gradually subsiding.


Subject(s)
Humans , Female , Middle Aged , Chemotherapy, Adjuvant , Rectal Neoplasms/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Gastrointestinal Stromal Tumors/drug therapy , Benzamides , Rectal Neoplasms/surgery , Gastrointestinal Stromal Tumors/surgery
16.
Indian J Cancer ; 2014 Jan-Mar; 51(1): 5-9
Article in English | IMSEAR | ID: sea-154271

ABSTRACT

INTRODUCTION: Imatinib is a bcr‑abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic phase, there is limited data on imatinib‑naïve advanced phase CML. MATERIALS AND METHODS: We retrospectively analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and blast crisis [BC]: 39), patients who received imatinib as frontline therapy. RESULTS: The median age of presentation in CML‑AP and CML‑BC were 32 years (12‑61) and 39 years (8‑59), respectively. Imatinib at 600 mg/day was initiated within 2 weeks of diagnosis. Median time to complete hematological response in both CML‑AP and CML‑BC was 3 months (CML‑AP: 1‑9 months and CML‑BC: 1‑14 months). At 6 months 30 (59%) CML‑AP and 15 (38%) CML‑BC patients achieved major cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete cytogenetic response, respectively. At a median follow‑up of 41 months, the median overall survival in CML‑AP was 61 months, but in CML‑BC it was 14 months. The median progression‑free survival and event‑free survival were 30 months and 23 months in CML‑AP and 14 and 12 months in CML‑BC, respectively. On univariate analysis, performance status (PS), spleen size, and MCyR predicted survival in AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non‑hematologic and hematologic adverse events were observed in 80% and 60% of patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity and interrupted in 30% for grade III toxicity. CONCLUSION: Front‑line imatinib is an option in advanced phases of CML especially in CML‑AP in low‑resource countries, where stem cell transplantation and alternate TKIs are not available.


Subject(s)
Adolescent , Adult , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Blast Crisis/drug therapy , Blast Crisis/mortality , Blast Crisis/pathology , Child , Drug Resistance, Neoplasm/drug effects , Female , Follow-Up Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Neoplasm Staging , Piperazines/therapeutic use , Prognosis , Pyrimidines/therapeutic use , Remission Induction , Retrospective Studies , Survival Rate , Young Adult
17.
Indian J Hum Genet ; 2014 Jan-Mar ;20 (1): 69-71
Article in English | IMSEAR | ID: sea-156636

ABSTRACT

Klinefelter syndrome (KS) is a sex chromosome disorder and has been reported to be associated with increased risk for malignancies. We report a 22‑year‑old male patient who was diagnosed to have chronic myeloid leukemia in chronic phase. Bone marrow cytogenetic examination revealed karyotype 47, XXY, t (9; 22)(q34, q11) suggestive of KS with presence of Philadelphia chromosome. The patient was treated with oral imatinib mesylate (400 mg/day). Complete hematological response was achieved after 2 months of therapy. The bcr‑abl/abl transcript percentage measured from peripheral blood at baseline, 1 and 2 years after imatinib were 97%, 1.99%, 0.007%, respectively. He remains in complete hematological and major molecular remission after 2 years of continued imatinib therapy.


Subject(s)
Humans , Klinefelter Syndrome/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Young Adult
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