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1.
Medicine (Baltimore) ; 100(11): e25111, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725990

RESUMO

ABSTRACT: Ustekinumab (UST) is approved for the treatment of moderate and severe Crohn disease (CD). Therapeutic drug monitoring (TDM) can help monitor the therapeutic effects of biologics. Therefore, the aim of this study was to evaluate the clinical outcomes of UST-treated CD patients and to determine the UST trough level in clinical and corticosteroid-free remission.This retrospective study included patients with moderate and severe active disease (AD) treated intravenously with a weight-adapted induction dose of UST. The maintenance therapy consisted of 90 mg UST subcutaneously at week 8 and thereafter every 8 or 12 weeks, depending on the clinical response. Clinical and corticosteroid-free remission, Harvey-Bradshaw-Index (HBI), UST trough level, and further laboratory parameters were measured just before the injection of UST at each follow-up evaluation until week 40.37 CD patients with a median HBI of 9 at week 0 were included in the study. Starting from 24% at the beginning of the monitoring period, and 38% of patients at the end of the monitoring period were treated with an 8-week interval (P = .18). There was a significant improvement in clinical (P = .0004), corticosteroid-free remission (P = .03), and HBI (P < .0001) from week 0 until the end of the observation period. The serum UST trough level decreased significantly from 2.0 at week 8 to 0.3, in the maintenance therapy and 0.4 µg/ml at the end of the therapy (P < .0001). Neither UST trough level nor levels of C-reactive protein (CRP) or fecal calprotectin (FC) were associated with disease outcome. Concomitant immunomodulator therapy did not appear to affect the UST trough level or clinical course.UST is an effective treatment option for difficult-to-treat patients with CD. UST trough levels may not be associated with treatment efficacy or the prediction of treatment outcomes in patients with CD. Further prospective randomized trials should be conducted to evaluate whether UST trough levels are associated with treatment outcomes in patients with CD.


Assuntos
Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos , Quimioterapia de Indução/estatística & dados numéricos , Quimioterapia de Manutenção/estatística & dados numéricos , Ustekinumab/sangue , Administração Intravenosa , Adulto , Biomarcadores/sangue , Doença de Crohn/sangue , Feminino , Humanos , Subunidade p40 da Interleucina-12/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/administração & dosagem
2.
Medicine (Baltimore) ; 100(11): e25188, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33726009

RESUMO

RATIONALE: The HLH-94 protocol is a standard induction treatment for hemophagocytic lymphohistiocytosis. However, about 30% of patients may not respond. Ruxolitinib has been clinically proven to be an effective treatment for hemophagocytic lymphohistiocytosis (HLH). PATIENT CONCERNS: A previously healthy 14-year-old girl presented to the local hospital with a 4-day history of persistent fever and sore throat. DIAGNOSIS: Clinical and laboratory tests revealed fever >38.5°C, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, and an elevated interleukin-2 receptor level. INTERVENTION: This patient was treated with ruxolitinib and the HLH-94 protocol. OUTCOMES: The patient's clinical and some laboratory indices improved. Unfortunately, vital signs such as respiratory function and consciousness did not improve. LESSONS: This case report highlights the effect of using ruxolitinib in conjunction with the HLH-94 protocol. However, safety evaluation of this regimen was not performed because critically ill patient died too fast.


Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pirazóis/administração & dosagem , Adolescente , Protocolos Clínicos , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/complicações , Etoposídeo/administração & dosagem , Evolução Fatal , Feminino , Humanos , Quimioterapia de Indução , Unidades de Terapia Intensiva , Linfo-Histiocitose Hemofagocítica/virologia , Metilprednisolona/administração & dosagem , Polietilenoglicóis/administração & dosagem , Resultado do Tratamento
3.
Medicine (Baltimore) ; 100(8): e24614, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663070

RESUMO

ABSTRACT: To investigate the prognostic value of the circulating peripheral blood cell counts changes in acute myeloid leukemia (AML) at different time points during induction chemotherapy.We retrospectively analyzed the clinical and laboratory data of 237 newly diagnosed AML patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2014.1. When primitive cells were first removed from the circulating peripheral blood, it was called peripheral blood blast clearance (PBBC). These patients were divided into two groups, according to PBBC. Statistical analysis showed that the day 5 of induction chemotherapy was a better cut-off for PBBC. PBBC≤5 days is defined as early-blast-clearance, while PBBC >6 days is delayed-blast-clearance. There was significant difference between the two groups on complete remission (CR) rate (P = .002), recurrence-free survival (RFS) (P = .026) and overall survival (OS) (P = .001). 2. Multivariate analysis suggested PBBC is an independent prognostic factor for CR, RFS, and OS in AML. Receiver operating characteristic(ROC) curve analysis showed the CR rate of patients with white blood cell count less than 1.25 × 109/L was significantly higher than that of patients with white blood cell count more than 1.25 × 10 9/L (P < .001) at day 5 of induction chemotherapy, but the RFS and OS was no significantly different (P > .05).The dynamics of peripheral blood blast in AML after initiation of induction chemotherapy, especially the time length to achieve PBBC, has important prognostic value for CR rate, RFS, and OS in AML patients. It is a simple and feasible method to evaluate the efficacy of AML.


Assuntos
Crise Blástica/patologia , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos/métodos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Adulto Jovem
4.
Medicine (Baltimore) ; 100(10): e24853, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725841

RESUMO

BACKGROUND: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events. METHODS: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. RESULTS: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups. DISCUSSION: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Imunossupressores/administração & dosagem , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Rituximab/administração & dosagem , Infecções Bacterianas/prevenção & controle , Teorema de Bayes , Esquema de Medicação , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Quimioterapia de Indução , Transplante de Rim/efeitos adversos , Doadores Vivos , Micoses/prevenção & controle , Metanálise em Rede , Viroses/prevenção & controle
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 56-61, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554797

RESUMO

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed.The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION: NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.


Assuntos
Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Fatores de Ligação ao Core , Intervalo Livre de Doença , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
6.
Medicine (Baltimore) ; 100(5): e24385, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592885

RESUMO

INTRODUCTION: The transformation of acute promyelocytic leukemia (APL) to acute mononuclear leukemia during treatment is a rare clinical phenomenon, and no CCAAT/enhancer-binding protein alpha (CEBPA) double mutations have been reported. PATIENT CONCERNS: A 42-year-old male was hospitalized for ecchymosis of the left lower limb for more than 1 month, gingival bleeding, and fatigue for 10 days, with aggravation of symptoms for 2 days. DIAGNOSIS: A diagnosis of APL was based on bone marrow (BM) morphology, immunophenotyping, fusion gene analysis, and fluorescence in situ hybridization. At a 1-year follow-up of maintenance treatment, he developed thrombocytopenia and was diagnosed with acute myeloid leukemia (AML) with a CEBPA double mutation by BM morphology, immunotyping, chromosomal analysis, polymerase chain reaction, and next generation sequencing. INTERVENTIONS: Complete remission of APL was achieved after all-trans retinoic acid and arsenic trioxide double induction therapy, followed by 2 cycles of mitoxantrone and cytarabine, and 1 cycle of idarubicin and cytarabine. Thereafter, sequential maintenance therapy of arsenic trioxide + all-trans retinoic acid + methotrexate was started. In the fourth cycle of maintenance therapy, APL was transformed into AML with a CEBPA double mutation. After 1 cycle of idarubicin and cytarabine, the patient achieved complete remission and received 3 cycles of idarubicin and cytarabine and three cycles of high-dose cytarabine as consolidation therapy. OUTCOMES: At present, the patient is in continuous remission with minimal residual disease negative for both of APL and AML. CONCLUSION: AML with a CEBPA double mutation after APL treatment is very rare, thus the prognosis of this event will require further observation.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Transformação Celular Neoplásica/genética , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Mutação
7.
Jpn J Clin Oncol ; 51(3): 333-344, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33506253

RESUMO

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Terapia Combinada , Humanos , Quimioterapia de Indução , Neoplasias Pulmonares/tratamento farmacológico , Estadiamento de Neoplasias
8.
Crit Rev Oncol Hematol ; 159: 103211, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33387628

RESUMO

This study aims to evaluate the efficacy and safety of Daratumumab-based induction therapy (DBI) in newly diagnosed multiple myeloma (MM). We identified four eligible RCTs including 2735 patients. The primary outcomes of RCTs involving transplant eligible (TEMM) and non-transplant eligible MM (NTEMM) were stringent complete response (sCR) and progression-free survival (PFS) respectively. Meta-analysis was performed using random-effects models. DBI improved sCR rates for standard risk (SR) (OR 1.86, 95 % CI 1.41-2.46) but not HiR (high risk) (OR 0.78, 95 % CI 0.41-1.48) (interaction P = 0.01) TEMM. In NTEMM, DBI improved PFS in SR (HR 0.44, 95 % CI 0.35-0.55) but not HiR patients. (HR 0.81, 95 % CI 0.52-1.27) (interaction P = 0.02). In conclusion, while DBI is efficacious in SR patients, there is insufficient data to support a benefit in HiR-MM.


Assuntos
Mieloma Múltiplo , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/uso terapêutico , Humanos , Quimioterapia de Indução , Mieloma Múltiplo/tratamento farmacológico
10.
J Clin Neurosci ; 84: 38-41, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33485596

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) is an uncommon disorder characterised by thunderclap headache and self-resolving angiographic vasospasm in the presence or absence of neurological deficit. We present the first case of RCVS likely precipitated by a complex array of confounding factors including a hyperosmolar hyperglycaemic state (HHS), induction chemotherapy with cyclophosphamide, non-Hodgkin's lymphoma, pancytopenia and previous blood transfusions. However, the clinical presentation in this case of altered conscious state followed by thunderclap headache was highly suggestive of HHS being the crucial inciting factor. This report of RCVS associated with HHS lends unique insight into key underlying pathophysiological mechanisms, and warns of the need to maintain a high index of suspicion for this elusive condition given the dynamic and transient nature of its clinical and radiological features.


Assuntos
Coma Hiperglicêmico Hiperosmolar não Cetótico/complicações , Vasoespasmo Intracraniano/etiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Transtornos da Cefaleia Primários/etiologia , Doença de Hodgkin/tratamento farmacológico , Humanos , Quimioterapia de Indução/métodos , Pessoa de Meia-Idade , Vincristina/administração & dosagem
11.
Lancet Haematol ; 8(1): e80-e93, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357487

RESUMO

This Review focuses on the use of 18F-fluorodeoxyglucose (18F-FDG) PET in the assessment of diffuse large B-cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma. PET is important for staging and prognostication with stage migration compared with CT. Better outcomes for patients with early stage diffuse large B-cell lymphoma and follicular lymphoma suggests better delineation of disease has translated to improved outcomes in such patients beyond simple stage migration. The aim of treatment of diffuse large B-cell lymphoma and peripheral T-cell lymphoma is potential cure, during which PET is mainly used to assess remission. Interim PET can assess chemosensitivity in these lymphomas, but it does not predict treatment success sufficiently well to enable treatment modification, particularly in the absence of more effective therapies for patients who remain PET-positive on interim scanning. In follicular lymphoma, traditionally viewed as an incurable lymphoma, the aim of treatment is to control disease for several years, while maintaining quality of life. PET can predict prognosis for patients with follicular lymphoma with high tumour burden at the end of induction chemotherapy, and it is being evaluated as a platform for response-adapted treatment of follicular lymphoma.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Quimioterapia de Indução , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico
12.
Lancet Gastroenterol Hepatol ; 6(2): 128-138, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33338442

RESUMO

BACKGROUND: The optimal preoperative treatment for locally advanced pancreatic cancer is unknown. We aimed to compare the efficacy and safety of nab-paclitaxel plus gemcitabine with nab-paclitaxel plus gemcitabine followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as multidrug induction chemotherapy regimens in locally advanced pancreatic cancer. METHODS: In this open-label, multicentre, randomised phase 2 study, done at 28 centres in Germany, eligible patients were adults (aged 18-75 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically or cytologically confirmed, treatment-naive locally advanced pancreatic adenocarcinoma, as determined by local multidisciplinary team review. After two cycles of nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients without progressive disease or unacceptable adverse events were randomly assigned (1:1) to receive either two additional cycles of nab-paclitaxel plus gemcitabine (nab-paclitaxel plus gemcitabine group) or four cycles of sequential FOLFIRINOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 180 mg/m2, fluorouracil 400 mg/m2 by intravenous bolus followed by a continuous intravenous infusion of 2400 mg/m2 for 46 h on day 1 of each 14-day cycle; sequential FOLFIRINOX group). Randomisation was done by the clinical research organisation on request of the trial centre using a permuted block design (block size 2 and 4). Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was surgical conversion rate (complete macroscopic tumour resection) in the randomised population by intention-to-treat analysis, which was assessed by surgical exploration in all patients with at least stable disease after completion of induction chemotherapy. This trial is registered with ClinicalTrials.gov, NCT02125136. FINDINGS: Between Nov 18, 2014, and April 27, 2018, 168 patients were registered and 130 were randomly assigned to either the nab-paclitaxel plus gemcitabine group (64 patients) or the sequential FOLFIRINOX group (66 patients). Surgical exploration after completed induction chemotherapy was done in 40 (63%) of 64 patients in the nab-paclitaxel plus gemcitabine group and 42 (64%) of 66 patients in the sequential FOLFIRINOX group. 23 patients in the nab-paclitaxel plus gemcitabine group and 29 in the sequential FOLFIRINOX group had complete macroscopic tumour resection, yielding a surgical conversion rate of 35·9% (95% CI 24·3-48·9) in the nab-paclitaxel plus gemcitabine group and 43·9% (31·7-56·7) in the sequential FOLFIRINOX group (odds ratio 0·72 [95% CI 0·35-1·45]; p=0·38). At a median follow-up of 24·9 months (95% CI 21·8-27·6), median overall survival was 18·5 months (95% CI 14·4-21·5) in the nab-paclitaxel plus gemcitabine group and 20·7 months (13·9-28·7) in the sequential FOLFIRINOX group (hazard ratio 0·86 [95% CI 0·55-1·36]; p=0·53). All other secondary efficacy endpoints, such as investigator-assessed progression-free survival, radiographic response rate, CA 19-9 response rate, and R0 resection rate, were not significantly different between the two treatment groups except for improved histopathological downstaging in evaluable resection specimens from the sequential FOLFIRINOX group (ypT1/2 stage: 20 [69%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·0003; ypN0 stage: 15 [52%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·02). Grade 3 or higher treatment-emergent adverse events during induction chemotherapy occurred in 35 (55%) of 64 patients in nab-paclitaxel plus gemcitabine group and in 35 (53%) of 66 patients in the sequential FOLFIRINOX group. The most common of which were neutropenia (18 [28%] in nab-paclitaxel plus gemcitabine group, 16 [24%] in the sequential FOLFIRINOX group), nausea and vomiting (two [3%] in nab-paclitaxel plus gemcitabine group, eight [12%] in the sequential FOLFIRINOX group), and bile duct obstruction with cholangitis (six [9%] in nab-paclitaxel plus gemcitabine group, seven [11%] in the sequential FOLFIRINOX group). No deaths were caused by treatment-related adverse events during the induction chemotherapy phase. INTERPRETATION: Our findings suggest that nab-paclitaxel plus gemcitabine is similarly active and safe as nab-paclitaxel plus gemcitabine followed by FOLFIRINOX as multidrug induction chemotherapy regimens for locally advanced pancreatic cancer. Although conversion to resectability was achieved in about a third of patients, additional evidence is required to determine whether this translates into improved overall survival. FUNDING: Celgene.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/uso terapêutico , Esquema de Medicação , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Quimioterapia de Indução , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento , Adulto Jovem
13.
Medicine (Baltimore) ; 99(51): e23719, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371122

RESUMO

ABSTRACT: Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25-6.07) months vs 3.98 (95%CI 3.71-4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04-0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38-25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23-23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21-1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oxaloacetatos/uso terapêutico , Administração Metronômica , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Intervalo Livre de Progressão
14.
N Z Med J ; 133(1527): 104-110, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33332332

RESUMO

Multiple myeloma is the second most common blood cancer in New Zealand with higher incidence in Maori and Pacific Island populations. It remains an incurable disease but the rapidly changing treatment landscape has led to improved outcome. In response to recent changes in funding of anti-myeloma therapy in New Zealand, the New Zealand Myeloma Interest Group has reviewed the latest literature and updated the treatment pathway of transplant-eligible patients with newly diagnosed multiple myeloma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Quimioterapia de Consolidação , Quimioterapia de Indução , Quimioterapia de Manutenção , Mieloma Múltiplo/terapia , Transplante de Medula Óssea/métodos , Bortezomib/administração & dosagem , Consenso , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Quimioterapia de Indução/métodos , Lenalidomida , Nova Zelândia , Guias de Prática Clínica como Assunto , Talidomida/administração & dosagem
15.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370944

RESUMO

A 59-year-old man with refractory Cronkhite-Canada syndrome (CCS) had poor clinical response to high-dose intravenous steroids, azathioprine, total parenteral nutrition and best supportive care. He remained highly symptomatic with abdominal pain, diarrhoea, recurrent sepsis and profound weight loss. Infliximab induction was given as rescue therapy, with marked clinical improvement observed within 3 weeks. This allowed steroid taper. Within 12 months of infliximab therapy, he achieved complete clinical remission and returned to his baseline weight and a full oral diet. Sequential endoscopies observed significant regression of previous marked gastrointestinal polyposis, including histological remission on colonic biopsies at 3.5 and 5 years of treatment. He currently remains in remission following 6 years of combination therapy with 5 mg/kg 8 weekly infliximab and azathioprine, and there is ongoing discussion with regard to the benefits and risks of therapy de-escalation. This case demonstrates the effectiveness of infliximab in inducing and maintaining remission in refractory CCS.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/farmacologia , Infliximab/uso terapêutico , Polipose Intestinal/tratamento farmacológico , Azatioprina/farmacologia , Azatioprina/uso terapêutico , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Resistência a Medicamentos , Fármacos Gastrointestinais/farmacologia , Gastroscopia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Infliximab/farmacologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Polipose Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/patologia , Resultado do Tratamento
16.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 55(12): 1143-1153, 2020 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-33342130

RESUMO

Objective: To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma. Methods: Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ(2)) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results: A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy (P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion: TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia , Cisplatino/uso terapêutico , Humanos , Quimioterapia de Indução , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
17.
BMC Infect Dis ; 20(1): 739, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032533

RESUMO

BACKGROUND: Invasive infections with Candida krusei are uncommon and rarely complicated by spondylitis. Previous described cases were solely treated with antimycotic therapy, despite guidelines recommending surgical interventions. CASE PRESENTATION: We describe a case of C. krusei spondylitis in a patient treated with chemotherapy for acute myeloid leukemia. After induction chemotherapy, the patient developed a candidemia, which was treated with micafungin. One month after the candidemia, the patient was admitted with severe lumbar pain. Spondylitis of the L4 and L5 vertebra was diagnosed on MR-imaging, with signs suggesting an atypical infection. The patient was treated with anidulafungin combined with voriconazole. Despite maximal conservative management symptoms gradually worsened eventually requiring surgical intervention. CONCLUSIONS: In contrast to previous case reports, antimycotic treatment alone could be insufficient in treating C. krusei spondylitis.


Assuntos
Candida/efeitos dos fármacos , Candidíase/imunologia , Hospedeiro Imunocomprometido , Espondilite/tratamento farmacológico , Espondilite/imunologia , Idoso , Anidulafungina/uso terapêutico , Antifúngicos/uso terapêutico , Candidemia/induzido quimicamente , Candidemia/tratamento farmacológico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/cirurgia , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Micafungina/uso terapêutico , Espondilite/microbiologia , Espondilite/cirurgia , Resultado do Tratamento , Voriconazol/uso terapêutico
18.
Acad Radiol ; 27(12): 1655-1664, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33004261

RESUMO

RATIONALE AND OBJECTIVES: To evaluate and compare the performance of radiomics in predicting induction chemotherapy response treated with two different regimens in patients with advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: A total of 265 patients with pathologically confirmed locally advanced nasopharyngeal carcinoma (stage II-IV), including 115 treated with gemcitabine plus cisplatin (GP group) and 150 treated with docetaxel plus cisplatin (TP group) were retrospectively enrolled. Radiomics features were extracted from the volume of interest delineated in multi-MR sequences on a 3T scanner. After random stratified grouping (training and validation cohorts) and logistic regression based on selected features, the association between the radiomics signature and the early response to induction chemotherapy were established for GP and TP regiments, respectively. RESULTS: Clinical factors showed no significant difference between the response and non-response groups for the GP and TP regiments (all p > 0.05). The accuracy of the radiomics signature consisting of selected features from the joint T1, T2, and T1C in the GP group (0.852 in the training cohort vs. 0.853 in the validation cohort) was significantly higher than that in the TP group (0.774 vs 0.727). The overall performance of the GP model was steady, with efficiency to distinguish responders from nonresponders with an AUC reaching 0.907 (95% confidence interval [CI] [0.843-0.970]) in the training cohort and 0.886 (95% CI [0.772-0.998]) in the validation cohort, while leveling at 0.800 (95% CI [0.712-0.888]) in the training cohort and 0.863 (95% CI [0.758-0.967]) in the validation cohort in the TP group. CONCLUSION: Pretreatment MR radiomics signature can better predict the early response to IC in the GP regimen than the TP regimen, which may be helpful to guide IC management.


Assuntos
Quimioterapia de Indução , Neoplasias Nasofaríngeas , Humanos , Imagem por Ressonância Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Estudos Retrospectivos
19.
PLoS One ; 15(10): e0236460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112882

RESUMO

The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.


Assuntos
Bactérias/classificação , Biodiversidade , Febre/microbiologia , Microbioma Gastrointestinal , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Neutropenia/microbiologia , Adolescente , Adulto , Idoso , Bactérias/isolamento & purificação , Feminino , Febre/induzido quimicamente , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Adulto Jovem
20.
N Engl J Med ; 383(17): 1613-1623, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33085860

RESUMO

BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment. METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment. RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%). CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.).


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dasatinibe/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia de Consolidação , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Mutação , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento
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