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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1440-1444, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067934

RESUMO

OBJECTIVE: To explore the efficacy and adverse reactions of decitabine combined with reduction FLAG regimen on the senile patients with high-risk AML. METHODS: 12 senile patients with high-risk AML received decitabine combined with reduced FLAG regimen (decitabine 20 mg/m2, intravenous drip, qd, d 1-5; fludarabine 30 mg/m2, intravenous drip lasts 30 min, qd, d 3-6; Ara-C 1 g/m2, intravenous drip, qd, d 3-6; and G-CSF 300 µg/d, subcu- taneous injection, d 2 to neutrophils reached the lowest return to>1.0×109/L) in our study. The efficacy and adverse reactions of this regimen were analyzed. RESULTS: 9 patients achieved complete remission(CR) after one course of decitabine combined with reduced FLAG regimen, 2 patients achieved partial remission (PR) and 1 patient reached a stable disease (SD). The overall response rate was 92%. The median follow-up period was 7.4 months ranged from 3 to 12 months. The median survival time for all patients was 6.4 months. The main treatment-related toxicities were myelosuppression and infection due to neutropenia. Severe non-hematologic toxicities were not observed in these patients, and there was no treatment-related mortality. CONCLUSION: Decitabine combined with reduced FLAG regimen has a definite clinical efficacy in the treatment of senile patients with high-risk AML. This regimen, as induction remission regimen, can effectively improve the CR rate and reduce the adverse reactions. Therefore, it may be used as one of the preferred induction remission regimen to treat the senile patients with high-risk AML.


Assuntos
Decitabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/uso terapêutico , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Resultado do Tratamento
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1516-1522, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067947

RESUMO

OBJECTIVE: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , China , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1551-1557, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067953

RESUMO

OBJECTIVE: To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time. METHODS: The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different. RESULTS: There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score<3 at diagnosis, and CR/PR after treatment could improve the survival time of patients. CONCLUSION: The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
4.
Medicine (Baltimore) ; 99(40): e22488, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019444

RESUMO

RATIONALE: Some acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of acute promyelocytic leukemia (APL) but without the typical promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement. Herein, we report an AML patient resembling APL but with nucleoporin 98/retinoid acid receptor gamma gene (NUP98/RARG) fusion transcript and Runt-related transcription factor 1 (RUNX1) mutation. PATIENT CONCERNS: An 18-year-old male presented at the hospital with a diagnosis of AML. DIAGNOSES: The patient was diagnosed with bone marrow examination. Bone marrow smear displayed 90.5% promyelocytes. Fluorescence in situ hybridization analysis failed to detect the PML/RARα fusion transcript or RARα amplification. While real-time polymerase chain reaction showed positivity for the NUP98/RARG fusion transcript. G-banding karyotype analysis showed a normal karyotype. INTERVENTIONS: The patient showed resistance to arsenic trioxide and standard 3 + 7 chemotherapy, but eventually achieved complete remission through the Homoharringtonine, Cytarabine, and Aclarubicin chemotherapy. OUTCOMES: These measures resulted in a rapid response and disease control. LESSONS: Acute myeloid leukemia with the NUP98/RARG fusion gene and the RUNX1 mutation may be a special subtype of AML and may benefit from the alkaloid-based regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Adolescente , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Diagnóstico Diferencial , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Promielocítica Aguda/diagnóstico , Masculino , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Receptores do Ácido Retinoico/genética
6.
Lancet Oncol ; 21(10): 1283-1295, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002436

RESUMO

BACKGROUND: HER2-positive metastatic breast cancer is incurable and new treatments are needed. Addition of atezolizumab to trastuzumab emtansine might potentiate anticancer immunity and enhance the HER2-targeted cytotoxic activity of trastuzumab emtansine. We aimed to test this combination in HER2-positive advanced breast cancer that had progressed after previous treatment with trastuzumab and a taxane. METHODS: The KATE2 study is a randomised, double-blind, placebo-controlled, phase 2 study at 68 centres from nine countries across Asia, Australia, North America, and western Europe. Eligible patients were adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and centrally confirmed, measurable, HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. Patients were randomly assigned (2:1) either trastuzumab emtansine (3·6 mg/kg of bodyweight) plus atezolizumab (1200 mg) or trastuzumab emtansine plus placebo; all study drugs were administered by intravenous infusion every 3 weeks. Randomisation was done via an interactive voice and web response system using a permuted block scheme (block size of six) and was stratified by PD-L1 status, world region, and liver metastases. Patients, investigators, and study team members were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02924883, and the study has been completed. FINDINGS: Between Sept 26, 2016, and Aug 7, 2017, 330 patients were screened for the study, of whom 202 were randomly allocated either atezolizumab (n=133) or placebo (n=69). At the recommendation of the independent data monitoring committee, treatment assignment was unmasked on Dec 11, 2017, due to futility and the numerically higher frequency of adverse events among patients assigned atezolizumab. This date was set as the clinical cutoff for the primary analysis. Median follow-up was 8·5 months (IQR 6·1-11·5) for patients assigned atezolizumab and 8·4 months (5·3-11·1) for those assigned placebo. Median progression-free survival was 8·2 months (95% CI 5·8-10·7) for patients assigned atezolizumab versus 6·8 months (4·0-11·1) for those assigned placebo (stratified hazard ratio 0·82, 95% CI 0·55-1·23; p=0·33). The most common grade 3 or worse adverse events were thrombocytopenia (17 [13%] among 132 patients who received atezolizumab vs three [4%] among 68 who received placebo), increased aspartate aminotransferase (11 [8%] vs two [3%]), anaemia (seven [5%] vs 0), neutropenia (six [5%] vs three [4%]), and increased alanine aminotransferase (six [5%] vs two [3%]). Serious adverse events occurred in 43 (33%) of 132 patients who received atezolizumab and 13 (19%) of 68 patients who received placebo. One patient who received atezolizumab died due to a treatment-related adverse event (haemophagocytic syndrome). INTERPRETATION: Addition of atezolizumab to trastuzumab emtansine did not show a clinically meaningful improvement in progression-free survival and was associated with more adverse events. Further study of trastuzumab emtansine plus atezolizumab is warranted in a subpopulation of patients with PD-L1-positive, HER2-positive advanced breast cancer. FUNDING: F Hoffman-La Roche.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/patologia , Método Duplo-Cego , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Análise de Sobrevida , Resultado do Tratamento
7.
BMJ Case Rep ; 13(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028572

RESUMO

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.


Assuntos
Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumonia Viral/diagnóstico , Sarcoma de Ewing , Tomografia Computadorizada por Raios X/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Exame de Medula Óssea/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Masculino , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
8.
Medicine (Baltimore) ; 99(35): e21922, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871929

RESUMO

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antitrombinas/uso terapêutico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna , Infarto da Artéria Cerebral Média/induzido quimicamente , Terapia Trombolítica , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Administração Oral , Trombose das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Dabigatrana/uso terapêutico , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico
9.
Medicine (Baltimore) ; 99(35): e21938, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871937

RESUMO

RATIONALE: Aggressive variant of splenic marginal zone lymphoma (AV-SMZL) is a very rare disease that is often associated with TP53 mutations and has a poor prognosis. On the other hand, recent advances in genome sequencing techniques enable us to understand the molecular characteristics of rare cancers such as AV-SMZL. Here we present a case of AV-SMZL analyzed using a genetic test. PATIENT CONCERNS: A 66-year-old woman was admitted with splenomegaly and lymphocytosis. Computed tomography revealed marked splenomegaly without lymphadenopathy in any other areas. The serum soluble interleukin-2 receptor (sIL-2R) level was significantly elevated. Peripheral and bone marrow blood tests showed an increase in abnormal lymphocytes. DIAGNOSIS: A splenectomy revealed an SMZL pattern with increased numbers of large cells and mitotic cells and a high Ki-67 positivity rate, which led to a diagnosis of AV-SMZL. Although TP53 mutation was not detected, mutations in NOTCH2, NCOA4, PTEN, EPHA3, and KMT2D were identified. Among these, the mutations in NCOA4, PTEN, and EPHA3 were novel pathogenic mutations in SMZL, which suggests they may be related to the aggressiveness and persistence of the disease. INTERVENTIONS: The patient was administered a rituximab-containing regimen and rituximab-maintenance therapy. OUTCOMES: The patient continues to exhibit a complete response. LESSONS: This is a case of AV-SMZL in which a cancer panel test successfully detected genetic alterations that are potentially associated with its pathogenesis. These findings suggest that genetic analysis is useful for making diagnoses as well as for determining treatment strategies in AV-SMZL.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Rituximab/uso terapêutico , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/tratamento farmacológico , Idoso , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/cirurgia , Mutação , Indução de Remissão , Esplenectomia , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/cirurgia
10.
Medicine (Baltimore) ; 99(35): e21848, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871908

RESUMO

RATIONALE: Drug-induced pancreatitis (DIP) is a kind of acute pancreatitis with a relatively low incidence. There are many cases of acute pancreatitis (AP) caused by chemotherapeutic agents that have been reported. However, few reports focus on the combination of chemotherapeutic agents that induce acute pancreatitis. This article aims to retrospectively analyze a case of DIP and to explore the relationship between chemotherapeutic agents and acute pancreatitis. PATIENT CONCERNS: Here, we report a 35-year-old Chinese female patient who was diagnosed as acute myeloid leukemia with BCR/ABL expression. After induction chemotherapy of daunorubicin and cytarabine, bone marrow aspiration showed: Acute myeloid leukemia-not relieved (AML-NR). Then the regimen of homoharringtonine, cytarabine and dasatinib was started. The patient developed abdominal pain on the 14th day of chemotherapy. Laboratory tests showed elevated serum amylase (AMY) and lipase (LIPA). Computed tomography (CT) of the abdomen revealed a swollen pancreas with blurred edges and thickened left prerenal fascia. DIAGNOSIS: The patient was diagnosed as DIP by the symptoms of upper abdominal pain and the change of CT images. Other common causes of AP were excluded meanwhile. INTERVENTIONS: The chemotherapy was stopped immediately. And after fasting, fluid infusion and inhibiting the secretion of the pancreas, the symptoms were relieved. OUTCOMES: DIP relapsed when the regimen of aclacinomycin + cytarabine + G-CSF + dasatinib regimen (G-CSF (400ug/day, day 1 to 15), cytarabine (30 mg/day, day 2 to 15), aclacinomycin (20 mg/day, day 2 to 5)and dasatinib (140 mg/day, continuously)) was given, and was recovered after treatment for AP was performed. LESSONS: To choose the best treatment plan for patients, clinicians should raise awareness of DIP, and should know that chemotherapeutic agents can induce pancreatitis and the combination of chemotherapeutic agents may increase the risk of drug-induced pancreatitis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Pancreatite/induzido quimicamente , Adulto , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Feminino , Mepesuccinato de Omacetaxina/administração & dosagem , Mepesuccinato de Omacetaxina/efeitos adversos , Humanos , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X
11.
Medicine (Baltimore) ; 99(33): e21440, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871991

RESUMO

RATIONALE: Follicular non-Hodgkin lymphoma (fNHL) is a neoplasm characterized by an indolent course and chemosensitivity, but also by disease recurrence. Bendamustine is often used as frontline treatment or second line. HEADING DIAGNOSIS:: fNHL. PATIENT CONCERNS: A 63-year-old Caucasian male with diagnosis of fNHL lymphoma underwent to cyclophosphamide, doxorubicin, vincristine, and prednisone associated with rituximab chemoimmunotherapy, during which interim reevaluation showed progressive disease and severe toxicity. INTERVENTIONS: Early switch to rituximab-bendamustine. OUTCOMES: This regimen was well tolerated, patient compliance was optimal, there were no delays in administration and no infectious episodes. An interim reevaluation after 3 courses revealed that the patient was fit, the blood cell count was normal, and lymphadenopathies and nocturnal sweating had completely regressed. Of note, the PET/CT scan did not show fluorodeoxyglucose pathological uptake, clearly confirming disease regression. LESSONS: Early switching to a bendamustine-rituximab-based scheme, even during conventional chemotherapy, decreases toxicity and reduces the risk of treatment interruption or delay, with favorable effects on overall response and prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Ciclofosfamida , Doxorrubicina , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona , Vincristina
12.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
Medicine (Baltimore) ; 99(33): e21743, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872062

RESUMO

INTRODUCTION: FOLFOX therapy is the main chemotherapy regimen for colorectal cancer. Peripheral neuropathy, hematotoxicity, and digestive symptoms are known to be the most frequent adverse events. Hyperammonemia and lactic acidosis rarely occur simultaneously during treatment with FOLFOX therapy; the number of case reports is limited worldwide. We report a case of disturbance of consciousness, considered to be caused by hyperammonemia and lactic acidosis that occurred during treatment with mFOLFOX6 therapy that was administered as postoperative adjuvant treatment for rectal cancer. PATIENT CONCERNS: This case was of a 71-year-old man who had been receiving oral treatment for chronic kidney disease and diabetes mellitus. Laparoscopic low anterior resection and artificial anal construction surgery were performed for stage III rectal cancer. As adjuvant postoperative therapy, mFOLFOX6 therapy was started but was followed by a disturbance of consciousness. DIAGNOSES: Results of the blood tests revealed notable hyperammonemia (ammonia level, 1,163 µg/dl) and lactic acidosis (pH 7.207; lactate, 17.56 mmol/L); however, imaging diagnosis did not reveal intracranial lesions that could cause disturbance of consciousness. INTERVENTIONS: For hyperammonemia, branched-chain amino acid agents and Ringers solution supplementation were administered. For acidosis, 7% sodium hydrogen carbonate was administered as treatment. OUTCOMES: The disturbance of consciousness improved within 12 hours of initiating the treatment, and the patient was discharged with no sequelae on 7th day after hospitalization. CONCLUSION: In patients with chronic kidney disease, FOLFOX regimen may confer risks of hyperammonemia and lactic acidosis.


Assuntos
Acidose Láctica/complicações , Antimetabólitos Antineoplásicos/efeitos adversos , Transtornos da Consciência/etiologia , Fluoruracila/efeitos adversos , Hiperamonemia/complicações , Acidose Láctica/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Hiperamonemia/induzido quimicamente , Masculino , Neoplasias Retais/tratamento farmacológico
14.
Anticancer Res ; 40(10): 5393-5397, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988858

RESUMO

BACKGROUND/AIM: We established a new patient-derived orthotopic xenograft (PDOX) model of gastric cancer liver metastasis and evaluated the efficacy of a novel combination chemotherapy, gemcitabine (GEM) plus 5-fluorouracil (5-FU), compared to a standard regimen of oxaliplatinum (L-OHP) plus 5-FU on the liver metastasis. MATERIALS AND METHODS: Patient-derived gastric cancer was established in nude mice from the patient' s surgical tumor specimen. A single tumor fragment was implanted in the liver of nude mice. The mice with tumors were treated by GEM plus 5-FU or L-OHP plus 5-FU. RESULTS: GEM plus 5-FU or L-OHP plus 5-FU significantly and similarly inhibited tumor growth on the liver compared to the untreated control (p=0.007, p=0.02, respectively). CONCLUSION: GEM plus 5-FU could be a novel future clinical alternative to L-OHP plus 5-FU in gastric cancer patients who cannot tolerate platinum drugs.


Assuntos
Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/farmacologia , Estômago/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Ann Hematol ; 99(11): 2589-2598, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892275

RESUMO

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos de Boro/administração & dosagem , Glicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Indução de Remissão , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
16.
Ann Hematol ; 99(11): 2577-2586, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32945942

RESUMO

Although treatment outcomes for diffuse large B cell lymphoma (DLBCL) have improved with the introduction of rituximab, approximately half of patients experience relapsed/refractory (r/r) disease. Furthermore, no standard salvage therapy has yet been established to date, while limitations in treatment options exist due to toxicity and restricted tolerability among elderly patients and/or those with comorbidities. The ICE (ifosfamide, cyclophosphamide, and etoposide) regimen is often used as salvage therapy for r/r DLBCL. Several modified ICE regimens not requiring continuous ifosfamide infusion are available, which can be used in outpatient clinics. This study analyzed the efficacy and toxicity of fractionated ICE with rituximab (f-R-ICE) as a salvage regimen among 47 patients with relapsed/refractory DLBCL (median age upon f-R-ICE initiation, 71 years). The whole cohort had an overall (ORR) and complete response rate of 53.1% (n = 25) and 25.5% (n = 12), respectively, and an estimated 1-year overall survival after f-R-ICE initiation of 57%. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI) upon f-R-ICE initiation. Patients with low CCI scores (68%) had a higher ORR than those with high CCI scores (36.4%) upon f-R-ICE initiation (P = 0.042). In contrast, no significant differences in overall survival (OS) were observed between the low and high CCI groups (1-year OS 56.6% vs. 52.2%; median OS 24 vs. 22.8 months) after initiating f-R-ICE. Our results suggest that f-R-ICE is a safe and effective salvage therapy for r/r DLBCL and can be used for older patients and/or those with high CCI scores in outpatient clinics.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Comorbidade , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Taxa de Sobrevida
17.
Lancet Haematol ; 7(10): e765-e771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976753

RESUMO

Over the past 30 years, the scientific community has made little progress in changing the natural history of peripheral T-cell lymphomas. Of the haematological malignancies, T-cell lymphomas have an extremely poor prognosis. One reason for this poor outcome has been that no treatment programme has ever been developed specifically for the broader category of the disease-peripheral T-cell lymphoma-let alone any of the specific subtypes, except advances made for patients with CD30-positive anaplastic large cell lymphoma. Decades of effort have focused on retrofitting chemotherapy programmes used for other diseases, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for diffuse large B-cell lymphoma, which have not been associated with much progress, and have universally produced far more toxicity than benefit. A remarkable heterogeneity, a paucity of cases, and the absence of peripheral T-cell lymphoma-specific drugs, until recently at least, have limited the field's ability to make substantive and innovative advances. Over the past few years, however, it appears the field is beginning to make progress. Lineage and disease-specific novel-to-novel platforms are producing, although perhaps not unsurprisingly, compelling results suggesting that the path to a cure for this rare orphan disease might be heading in a different direction.


Assuntos
Linfoma de Células T Periférico/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Imunoterapia/métodos , Medicina de Precisão/métodos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
18.
Ann Hematol ; 99(11): 2629-2637, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980890

RESUMO

Treatment of acute lymphoblastic leukemia (ALL) requires the combination of multiple drugs to integrate a complete remission. The different prognostic factors (age, leukocytes, risk, cytogenetic alterations) allow identifying those patients with a high risk of relapse, but there are few described factors that impact the induction response. The objective was to identify the utility of different risk factors (overexpression of the ABCB1 drug resistance gene, favorable response to steroids (FRS) and early response at day + 8 of treatment) on the percentage of complete remissions and overall survival. This is a prospective, observational study in adult patients with B-ALL without specific cytogenetic alterations, who started induction treatment based on a pretreatment with prednisone and subsequently vincristine (1.6 mg/m2 subcutaneous) plus daunorubicin (45 mg/m2 subcutaneously) on days + 1, + 8, + 15. The ABCB1 resistance gene was evaluated at diagnosis, the FRS at the end of the pretreatment and the early response during day + 8. A total of 53 adult patients diagnosed with ALL Philadelphia negative chromosome (Ph-), with immunophenotype B, with a normal karyotype, were studied. Cases with genetic abnormalities with a poor prognosis were excluded in order to reduce bias. The mean age was 48 years (range 17-68 years). 62.3% of patients were at high risk of relapse. When analyzing the risk factors, 30.2% showed high levels of the ABCB1 resistance gene, without showing an impact on the induction response (OR: 1.218, p = 0.743), but its overexpression was associated with a poor response to steroids as in the absence of early response. Individually, both the FRS (OR: 5.7, p = 0.004) and the absence of early response to day + 8 (OR: 6.42, p = 0.002) showed significance. By combining the different factors, having more than 2 was directly related to a failure (OR: 9.514, p = 0.000). The identification of factors such as FRS such as the persistence of blasts at the end of the first week of treatment is useful to identify patients at risk of failure in induction.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Quimioterapia de Indução , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Adolescente , Adulto , Idoso , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagem
19.
N Engl J Med ; 383(13): 1218-1230, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32945632

RESUMO

BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance. METHODS: In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety. RESULTS: Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively. CONCLUSIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Análise de Sobrevida , Neoplasias Urológicas/mortalidade , Urotélio
20.
Orv Hetil ; 161(38): 1623-1628, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32924966

RESUMO

Maintenance therapy has been the strong and standard element of many acute lymphoblastic leukaemia protocols, used much less frequently and systematically in adult oncohematological disorders. The first adult maintenance efforts appeared in follicular and mantle cell lymphoma (mostly monoclonal antibody based), along with an early maintenance effort to prolong the plateau phase of myeloma. For the time being, after a long debate, the prognosis-dependent type of consolidation and maintenance became - sometimes until relapse - the standard approach in myeloma patients. The so-called small molecules, which turned out to be effective as induction and relapse agents, are continuously moving toward maintenance settings. Moreover, maintenance efforts seem to be more and more considered and used in transplanted or some non-transplanted acute myeloid leukaemia patients as well. Nevertheless, maintenance should be patient-friendly, easy to use (e.g., tablets) by enabling short outpatient office time, done not very frequently, and as much quality-of-life-based as possible. Orv Hetil. 2020; 161(38): 1623-1628.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Humanos , Leucemia Mieloide Aguda/patologia , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
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