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1.
Intern Med ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34707049

RESUMO

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), significantly reduces mortality and morbidity in patients with chronic heart failure with a reduced ejection fraction (HFrEF). However, a considerable number of patients treated with sacubitril/valsartan experience hypotension, oliguria, progressive azotemia, and renal failure as adverse events. These issues have been linked to significant gaps in the usage and dosing of guideline-directed medical therapy with ARNI in patients with HFrEF. We herein report a relevant case of pathologically proven acute tubular necrosis after the first dose of sacubitril/valsartan, highlighting the importance of optimizing the medical therapy in an outpatient with HFrEF.

2.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638817

RESUMO

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.


Assuntos
Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Mamárias Experimentais/terapia , Tolerância a Radiação/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Tolerância a Radiação/imunologia , Tolerância a Radiação/efeitos da radiação
3.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500557

RESUMO

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Mebendazol/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo
4.
J Vasc Surg Venous Lymphat Disord ; 8(5): 741-747, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32113855

RESUMO

OBJECTIVE: Although rivaroxaban has recently become widely used for thrombosis treatment, it is difficult for clinicians to make clinical decisions in critical situations, such as emergent surgery or interventions, because a specific anti-Xa assay is not available in many laboratories. This study assessed the relationships between rivaroxaban-specific anti-factor Xa activity (AXA) and unfractionated heparin (UFH)-specific AXA and determined the cutoff level for UFH-specific AXA in critical situations for patients undergoing rivaroxaban therapy. METHODS: Thirty-eight blood samples were collected from patients with cancer-associated thrombosis receiving rivaroxaban therapy. All samples were assessed using both rivaroxaban-specific and UFH-specific anti-Xa assays. Routine coagulation studies, including prothrombin time (PT) and activated partial thromboplastin time, were also conducted on the samples. RESULTS: A positive dose-dependent correlation between rivaroxaban-specific and UFH-specific AXA was evident (R = 0.97; P < .0001). Rivaroxaban-specific AXA was also positively correlated with PT (R = 0.95; P < .0001) but only weakly with activated partial thromboplastin time (R = 0.67; P < .0001). Patients with plasma rivaroxaban concentrations <100 ng/mL were found to have UFH-specific AXA <1.41 IU/mL and PT <17.3 seconds, with sensitivities of 100% and 93.3% and specificities of 87.0% and 95.7%, respectively. CONCLUSIONS: Our study demonstrates that UFH-calibrated AXA correlates strongly with plasma rivaroxaban concentration. This assay appears to be sensitive to the presence of rivaroxaban, which may be advantageous in the setting of assessing drug levels for critical events. These findings suggest that if a rivaroxaban-specific anti-Xa assay is unavailable, the chromogenic anti-Xa assay for UFH may be useful to assess the anticoagulant effects of rivaroxaban.


Assuntos
Anticoagulantes/farmacologia , Testes de Coagulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Monitoramento de Medicamentos , Inibidores do Fator Xa/sangue , Heparina/farmacologia , Rivaroxabana/sangue , Tromboembolia Venosa/tratamento farmacológico , Idoso , Tomada de Decisão Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
5.
Medicine (Baltimore) ; 98(52): e18390, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876710

RESUMO

RATIONALE: Granulocytic sarcoma (GS), also known as chloroma, is a tumor comprising myeloblasts or monoblasts, potentially occurring as an extramedullary mass. Systemic chemotherapy should be used to induce complete remission. However, such patients with chloroma have a poorer treatment outcome than those without extramedullary myeloid sarcomas. PATIENT CONCERNS: A 30-year-old woman who initially presented with bilateral ovarian masses and splenomegaly was admitted to hospital. Also, her complete blood cell counts showed pancytopenia and blood smear revealed a few immature cells (3%). DIAGNOSES: A bone marrow biopsy demonstrated acute myelomonocytic leukemia, and the chromosomal analysis revealed a 46, XX, del18 (p11) [20] karyotype and cytogenetics and molecular markers showed all negative results. INTERVENTIONS: Since this diagnosis, she received remission-inducing chemotherapy comprising anthracycline and cytarabine, which is a standard regimen for acute myeloid leukemia (AML), and followed by allogenic hematopoietic stem cell transplantation from Human leukocyte antigen (HLA)-identical sibling donor. OUTCOMES: After transplantation, the bone marrow engrafted successfully without complications. She visited our clinic regularly with no evidence of leukemia relapse or graft-versus host disease. LESSONS: This report represents the first case of ovarian GS, wherein treatment was successful with high-dose chemotherapy, followed by allogenic hematopoietic stem cell transplantation without oophorectomy.


Assuntos
Leucemia Mieloide Aguda/terapia , Neoplasias Ovarianas/etiologia , Sarcoma Mieloide/etiologia , Transplante de Células-Tronco , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/terapia , Transplante de Células-Tronco/métodos
6.
Medicine (Baltimore) ; 98(25): e15882, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232923

RESUMO

RATIONALE: Primary immune thrombocytopenia (ITP) is an immune-mediated disease that is defined as increased platelet destruction and impaired platelet production. Treatment is recommended for highly selected patients, the standard regimen includes glucocorticoid, intravenous immunoglobulin (IVIG). The recombinant thrombopoietin (TPO) receptor agonists, romiplostim, stimulate platelet production and have approved for glucocorticoid or IVIG, splenectomy-refractory chronic ITP patients. PATIENT CONCERNS: A patient has been diagnosed with ITP, reftractory to steroid, IVIG, splenectomy, danazol, and cyclosporine. The patient received romiplostim to normalize his platelet count, however, over the course of the following year, his platelet counts progressively decreased despite increasing the romiplostim dosing. DIAGNOSES: A peripheral blood smear showed a severe leukoerythroblastic reaction and bone marrow biopsy demonstrated myelofibrosis due to romiplostim. OUTCOMES: Since this diagnosis, romiplostim was discontinued for a while, after 3 months, romiplostim was re-administered to improve thrombocytopenia. His platelet count recovered to 70,000/mm after the administration of romiplostim at 2 µg/kg, and he did not experience complications for 6 months. LESSONS: This report represents the first evidence of romiplostim-induced myelofibrosis, which was associated with increased levels of bone marrow reticulin and Masson trichrome staining.


Assuntos
Mielofibrose Primária/diagnóstico , Receptores de Trombopoetina , Proteínas Recombinantes de Fusão/efeitos adversos , Trombocitopenia/tratamento farmacológico , Trombopoetina/efeitos adversos , Medula Óssea , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/induzido quimicamente , Receptores Fc
7.
Medicine (Baltimore) ; 98(5): e14278, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702591

RESUMO

Sedation therapy is a potential solution to providing relief from refractory symptoms at end of life. The aim of this study was to investigate actual sedation practice and physician characteristics associated with the use of sedation for terminally ill cancer patients in South Korea.A retrospective review was conducted on consecutive patients who had died from cancer at seven tertiary medical centers between January 2010 and October 2015. The use of sedation was defined as the administration of sedative agents to relieve intolerable symptoms within the last 2 weeks preceding death. Patients and physician characteristics and information on the use of sedation were collected.A total of 8309 patients were included in the study. Sedatives were administered in 1334 patients (16.1%) for the following indications: delirium in 39.3%, intractable pain in 23.1%, and dyspnea in 21.9%. Median duration of sedation from initiation to death was 3 days. The use of sedation depended on physician specialty and experience. Family physicians used sedation most often (57.6%), followed by medical oncologists (13.9%), other internists (10.7%), and surgical oncologists (9.4%). The use of sedation was highest for physicians with >5 to 10 years practice experience (22.1%) and lowest for those in practice for 5 years or less (10.2%). The proportion of patients receiving sedation also varied markedly across participating institutions (range, 7.0%-49.7%).This large cohort study provides insight into sedation practice for terminally ill cancer patients in South Korea. Our study shows that the use of sedation depends on physician background and institution. A nation-wide guidelines and continued education on end-of-life sedation are required in South Korea.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Neoplasias/epidemiologia , Cuidados Paliativos/métodos , Padrões de Prática Médica/estatística & dados numéricos , Assistência Terminal/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Doente Terminal
8.
Biol Blood Marrow Transplant ; 24(12): 2471-2478, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30064012

RESUMO

Natural killer (NK)/T cell lymphoid malignancy comprises extranodal NK/T cell lymphoma (ENKTL) and aggressive NK cell leukemia (ANKL), and the outcomes for advanced or relapsed/refractory ENKTL and ANKL remain poor. Allogeneic stem cell transplantation (SCT) can be used as a frontline consolidation treatment to prevent the relapse of advanced disease or as salvage treatment after chemotherapy for relapsed sensitive disease. We retrospectively analyzed 36 patients (ENKTL, n = 26; ANKL, n = 10) who underwent upfront (n = 19) and salvage allogeneic SCT (n = 17) at 6 hospitals. Patients received myeloablative (n = 25) or reduced-intensity (n =11) conditioning regimens depending on the institute's policy. The median age at the time of allogeneic SCT was 37 years (range, 17 to 62), and more patients with ANKL (8/10) received upfront allogeneic SCT than ENKTL patients (11/26). Disease status before allogeneic SCT, conditioning regimen, and donor source did not differ between upfront and salvage allogeneic SCT groups. Febrile neutropenia (n = 20) and acute graft-versus-host disease (n = 16) were common adverse events. The median overall survival (OS) and progression-free survival (PFS) after allogeneic SCT were 11.8 months and 10.0 months, respectively. Twelve patients died from disease relapse and 12 from nondisease-related causes. Ten deaths occurred within 100 days after allogeneic SCT (10/24); these were mostly related to disease relapse (n = 8). The OS after allogeneic SCT did not differ between ENKTL and ANKL (P = .550) or between upfront and salvage SCT (P = .862). Complete chimerism was significantly associated with better PFS (P < .001). No significant differences in PFS were observed based on the conditioning regimen or source of stem cells (P > .05). Allogeneic SCT may be beneficial for patients with ENKTL and ANKL given that some patients were able to maintain their remission after allogeneic SCT. However, allogeneic SCT should only be performed in highly selected patients because the risks of disease relapse and nondisease-related mortality remain high.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfoide/terapia , Células T Matadoras Naturais/metabolismo , Terapia de Salvação/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Feminino , Humanos , Leucemia Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/patologia , Adulto Jovem
9.
J Palliat Med ; 21(9): 1367-1370, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30070936

RESUMO

Opioid addiction, although uncommon in cancer patients, can be a significant challenge for optimal pain management in certain patients. We present a case of a 59-year-old man with advanced colon cancer whose compulsive craving for the buccal tablet of fentanyl citrate (BTFC) was improved with the use of olanzapine. He was hospitalized for abdominal pain caused by disease progression. He had visited several times at outpatient follow-up to obtain a prescription for BTFC because he took all medications before the appointed times. After admission, intravenous infusion of oxycodone and opioid rotation were applied to the patient to control his pain. However, he complained that the pain was not relieved at all and persistently asked for only BTFC 7 to 15 times per day. With the diagnosis of opioid addiction, the transdermal buprenorphine patch was applied, but was ineffective for controlling the addictive behaviors. Finally, olanzapine (10 mg/day per os), a dopamine receptor antagonist, was given to control the craving behavior because psychological dependence is mediated by the dopaminergic system. Three days later, opioid craving was reduced from five to one on a 5-point Likert scale. The pain was well controlled to numeric rating scale 1 or 2 without cravings for BTFC. Craving behavior as a result of opioid addiction may be controlled with olanzapine. Further prospective studies on this issue are warranted.


Assuntos
Dor do Câncer/tratamento farmacológico , Fissura/efeitos dos fármacos , Olanzapina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor
10.
Cancer Res Treat ; 50(4): 1458-1461, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29361819

RESUMO

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Fibrossarcoma/tratamento farmacológico , Mixossarcoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cuidados Paliativos , Resultado do Tratamento
11.
Clin Respir J ; 12(3): 1264-1273, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28618180

RESUMO

OBJECTIVES: To identify the factors that predict the progression of radiological radiation pneumonitis (RP) to symptomatic RP, and to evaluate the usefulness of the neutrophil-lymphocyte ratio (NLR) as a marker of RP severity and prognosis in stage III non-small cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively reviewed 61 patients treated between January 2010 and December 2015. Patients' demographic characteristics, clinical data, laboratory findings and treatment parameters were analyzed to determine the predictive factors associated with progression from radiological RP to symptomatic RP. RESULTS: Forty-seven patients (77%) exhibited radiological RP at a median of 78 days after radiation therapy (RT) completion, and 15 (32%) of these patients developed symptomatic RP. The interval between RT completion and radiological RP presentation was shorter in patients who progressed to symptomatic RP (P = .001); progression was highly probable if this latency period was ≤2 months (P = .002). Stage and RT technique correlated with symptomatic RP development (P = .046 and P = .046, respectively). Among dosimetric factors, a V20 (defined as the lung volume receiving ≥20 Gy) of >30% was the most significant predictor of symptomatic RP (P = .001). The NLR and C-reactive protein level at radiological RP were higher in patients who developed symptomatic RP (P = .067 and P = .012, respectively). On multivariate analysis, a V20 >30% and an NLR at radiological RP >6 were associated with symptomatic RP development. CONCLUSION: The NLR at radiological RP is a useful biomarker for predicting symptomatic RP development after CCRT in stage III NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Linfócitos/citologia , Neutrófilos/citologia , Lesões por Radiação/sangue , Pneumonite por Radiação/sangue , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Lesões por Radiação/etiologia , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
12.
Cancer Res Treat ; 50(3): 791-800, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28838033

RESUMO

Purpose: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. Materials and Methods: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. Results: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). Conclusion: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/terapia , Cuidados Paliativos/métodos , Idoso , Idoso de 80 Anos ou mais , Aspartato Aminotransferases/metabolismo , Neoplasias do Sistema Biliar/metabolismo , Bilirrubina/metabolismo , Antígeno Carcinoembrionário/metabolismo , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Tamanho da Amostra , Albumina Sérica Humana/metabolismo , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
13.
Oncologist ; 22(11): 1354-1361, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28687626

RESUMO

BACKGROUND: To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS: Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS: No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. CONCLUSION: Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. IMPLICATIONS FOR PRACTICE: In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.


Assuntos
Corticosteroides/administração & dosagem , Dexametasona/administração & dosagem , Metilprednisolona/administração & dosagem , Neoplasias/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Dexametasona/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Soluço/induzido quimicamente , Soluço/prevenção & controle , Humanos , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Neoplasias/complicações , Vômito/tratamento farmacológico , Vômito/patologia
14.
Oncotarget ; 8(29): 47007-47019, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28388585

RESUMO

BACKGROUNDS: Sarcopenia is known to be associated with poor clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). There is no consensus concerning the optimal method to define sarcopenia in DLBCL. METHODS: We retrospectively reviewed 193 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Sarcopenia was classified by the region where the pretreatment skeletal muscle index (SMI) was measured. RESULTS: Both the sarcopenia-L3 and sarcopenia-pectoralis muscle (PM) groups had increased incidences of severe treatment-related toxicities and treatment discontinuation compared with the non-sarcopenia-L3 and non-sarcopenia-PM groups, respectively. The sarcopenia-L3 and non-sarcopenia-L3 groups had 5-year overall survival (OS) rates of 40.5% and 67.8% (p < 0.001), respectively. The sarcopenia-PM and non-sarcopenia-PM groups had 5-year OS rates of 35.9% and 69.0% (p < 0.001), respectively. When the sarcopenia-L3 alone and sarcopenia-PM alone groups were compared, there were no differences in baseline characteristics, treatment toxicity, or survival. In multivariate analysis, when compared with the non-sarcopenia-both group, OS was significantly worse in the sarcopenia-both group (HR, 2.480; 95% CI, 1.284 - 4.792; p = 0.007), but not in patients with either sarcopenia-L3 alone or sarcopenia-PM alone (p = 0.151). CONCLUSIONS: L3- and PM-SMIs are equally useful to define sarcopenia, which is related to intolerance to R-CHOP therapy and to worse survival in patients with DLBCL. More prognostic information can be obtained when these two SMIs are combined to define sarcopenia.


Assuntos
Músculos do Dorso/patologia , Região Lombossacral , Linfoma Difuso de Grandes Células B/complicações , Músculos Peitorais/patologia , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab , Sarcopenia/mortalidade , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
15.
Chin J Cancer ; 36(1): 9, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28086990

RESUMO

BACKGROUND: The optimal treatment strategy for biliary tract cancer (BTC) after curative-intent resection remains controversial. The purpose of this study was to evaluate the efficacy of fluoropyrimidine-based adjuvant chemotherapy for BTC patients undergoing microscopically margin-negative (R0) resection. METHODS: We retrospectively analyzed the clinical data of BTC patients who underwent curative-intent R0 resection. Patients were eligible if they received either fluoropyrimidine-based adjuvant chemotherapy or observation after R0 resection. RESULTS: A total of 153 patients were included. In the entire patient cohort, no significant differences were observed in 5-year overall survival (OS) rates (48.4% vs. 39.6%, P = 0.439) or 3-year recurrence-free survival (RFS) rates (49.1% vs. 39.5%, P = 0.299) between patients who received fluoropyrimidine-based adjuvant chemotherapy or observation. However, for patients with stages II and III BTC, chemotherapy significantly improved 5-year OS rate (52.4% vs. 35.6%, P = 0.002) and 3-year RFS rate (55.5% vs. 39.1%, P = 0.021) compared with observation. CONCLUSION: Fluoropyrimidine-based adjuvant chemotherapy may prolong the survival of patients with stages II and III BTC after R0 resection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Pirimidinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/patologia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Conduta Expectante
16.
Cancer Chemother Pharmacol ; 79(1): 99-106, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27928598

RESUMO

PURPOSE: There is still debated regarding the optimal treatment strategy for cholangiocarcinoma (CC) after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected intrahepatic and perihilar CCs. METHODS: We retrospectively reviewed the patients who underwent R0 resection for intrahepatic and perihilar CCs between January 2001 and December 2013 at six tertiary medical centers; adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of our study were recurrence-free survival (RFS) and overall survival (OS). RESULTS: We included a total of 137 consecutive patients in the analysis; 58.4% of them had intrahepatic CCs, and 25.5% had lymph node (LN) involvement. Seventy-three patients (53.3%) had received adjuvant therapy (CT, CRT, RT: 48, 13, 12, respectively), and most patients who had received adjuvant therapy had stage III or IVA, T3 or 4 tumors, and positive LNs. Multivariable analysis identified positive LN [hazard ratio (HR) 3.47; P < 0.001] and high baseline CA 19-9 level (HR 1.82; P = 0.027) as predictors of decreased OS. The effects of adjuvant therapy varied according to the treatment modality; adjuvant CRT showed significantly longer RFS than surgery only (HR 0.44; P = 0.036), with a nonsignificant trend for better OS (HR 0.46; P = 0.115). CONCLUSIONS: Adjuvant CT and RT were not associated with a survival advantage in R0-resected intrahepatic and perihilar CCs. CRT appears to be appropriate treatment after complete resection.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Quimiorradioterapia Adjuvante , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Acta Haematol ; 136(3): 186-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27623181

RESUMO

BACKGROUND: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. METHODS: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. RESULTS: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. CONCLUSIONS: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.


Assuntos
Doença de Hodgkin/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Humanos , Linfoma/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem
18.
Clin Sarcoma Res ; 6: 8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27175275

RESUMO

BACKGROUND: Angiosarcoma is a rare subgroup of soft tissue sarcomas associated with poor prognosis, but paclitaxel has been shown to be active in pretreated metastatic disease. We investigated the efficacy and safety of weekly paclitaxel as first-line chemotherapy in adult patients with metastatic angiosarcoma. METHODS: A retrospective study using the Samsung Medical Center (Seoul, Korea) cancer chemotherapy registry was performed on 21 consecutive patients with angiosarcoma who were treated with weekly paclitaxel as first-line therapy for metastatic disease between Oct. 2008 and Dec. 2014. We excluded patients who were enrolled in clinical trials to ensure the results would reflect the real-world outcomes obtained in a daily clinical setting. Endpoints included efficacy in terms of response rate, progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Among 21 patients, 15 (71 %) were male and the median age was 53 years (range, 24-76). Primary sites of angiosarcoma were the visceral organs (33 %), scalp (29 %) and heart (23 %). The median number of metastatic sites was two (range, 1-5) with the lungs being the most frequently involved site. Weekly paclitaxel was generally well tolerated: the major hematologic toxicity was grade 1/2 anemia (24 %). Among non-hematologic toxicities, grade 1/2 peripheral neuropathy was most commonly observed (67 %). Objective response was observed in 11 (52 %) patients (4 complete and 7 partial responses). With a median follow-up of 21 months, the estimated median PFS and OS were 5.7 months (95 % CI 5.1-6.3) and 18.6 months (95 % CI 9.9-27.3), respectively. CONCLUSIONS: In this retrospective study, first-line chemotherapy with weekly paclitaxel demonstrated clinically relevant efficacy and tolerability in unselected Korean patients with metastatic angiosarcoma. It is encouraging that response rate and PFS for Korean patients were similar to those reported in Western reports.

19.
Oncotarget ; 7(28): 43492-43503, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27224918

RESUMO

Monocarboxylate transporters (MCTs) play a major role in up-regulation of glycolysis and adaptation to acidosis. However, the role of MCTs in gastric cancer (GC) is not fully understood. We investigated the potential utilization of a new cancer therapy for GC. We characterized the expression patterns of the MCT isoforms 1, 2, and 4 and investigated the role of MCT in GC through in vitro and in vivo tests using siRNA targeting MCTs. In GC cell lines, MCT1, 2, and 4 were up-regulated with different expression levels; MCT1 and MCT4 were more widely expressed in GC cell lines compared with MCT2. Inhibition of MCTs by siRNA or AR-C155858 reduced cell viability and lactate uptake in GC cell lines. The effect of inhibition of MCTs on tumor growth was also confirmed in xenograft models. Furthermore, MCT inhibition in GC cells increased the sensitivity of cells to radiotherapy or chemotherapy. Compared with normal gastric tissue, no significant alterations of expression levels in tumors were identified for MCT1 and MCT2, whereas a significant increase in MCT4 expression was observed. Most importantly, MCT4 was highly overexpressed in malignant cells of acsites and its silencing resulted in reduced tumor cell proliferation and lactate uptake in malignant ascites. Our study suggests that MCT4 is a clinically relevant target in GC with peritoneal carcinomatosis.


Assuntos
Antineoplásicos/uso terapêutico , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Tiofenos/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Ácido Láctico/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/radioterapia , Neoplasias Peritoneais/secundário , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Simportadores/genética , Simportadores/metabolismo , Tiofenos/farmacologia , Regulação para Cima , Uracila/farmacologia , Uracila/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Cachexia Sarcopenia Muscle ; 7(5): 567-576, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27104110

RESUMO

BACKGROUND: Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). RESULTS: Treatment-related mortality (21.7 vs. 5.0%, P = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group (P < 0.001). The 5 year OS rates were 37.3% in the sarcopenic group and 68.1% in the non-sarcopenic group (P < 0.001). Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P = 0.009; revised-IPI, 0.74, P < 0.001; National Comprehensive Cancer Network-IPI, 0.77, P = 0.062). CONCLUSIONS: Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Sarcopenia/etiologia , Sarcopenia/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rituximab , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
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