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1.
Medicine (Baltimore) ; 99(10): e19360, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150078

RESUMO

BACKGROUND: A systemic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy, toxicity and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Research searching was performed in Web of Science, PubMed, The Cochrane Library, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database for Chinese Technical Periodicals and Wanfang Database. RCTs including patients diagnosed with locoregionally advanced NPC without metastasis and randomly treated with IC plus CCRT and CCRT alone were included. Survival and outcome data were extracted and meta-analysis was performed using the Revman 5.3.0 software. RESULTS: Ten RCTs (2280 patients) were selected and used for pooled meta-analysis. In comparison with CCRT, IC plus CCRT treatment significantly improved the overall survival (OS; HR = 0.70, 95%CI 0.56-0.87, P = .002), progression-free survival (PFS; HR = 0.75, 95%CI 0.65-0.87, P < .0001), distant metastasis failure-free survival (DMFS; HR = 0.71, 95%CI 0.58-0.85, P = .0003) and loco-regional failure-free survival (LFES; HR = 0.72, 95%CI 0.59-0.88, P = .002) of patients with locoregionally advanced NPC. Patients treated with IC and CCRT had higher incidence of grade 3-4 leucopenia and thrombocytopenia than patients treated with CCRT alone (P < .0001). No significant difference in other grade 3-4 adverse events and radiation toxicity was observed between the two groups. IC combined with CCRT improved the survival of patients with locoregionally advanced NPC. CONCLUSIONS: Combined IC and CCRT therapy was an efficacy treatment regimen for locoregionally advanced NPC.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia de Indução/normas , Neoplasias Nasofaríngeas/tratamento farmacológico , Terapia Combinada , Humanos , Quimioterapia de Indução/métodos , Quimioterapia de Indução/tendências , Neoplasias Nasofaríngeas/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
2.
Cancer Treat Rev ; 85: 101995, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113080

RESUMO

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Biópsia por Agulha , Quimiorradioterapia/métodos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
N Engl J Med ; 382(12): 1124-1135, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32130806

RESUMO

BACKGROUND: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Piridonas/administração & dosagem , Rilpivirina/administração & dosagem , Administração Oral , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , HIV-1/genética , Humanos , Quimioterapia de Indução , Injeções Intramusculares , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mutação , Medidas de Resultados Relatados pelo Paciente , Piridonas/efeitos adversos , Piridonas/sangue , RNA Viral/sangue , Rilpivirina/efeitos adversos , Rilpivirina/sangue , Carga Viral
4.
Artigo em Chinês | MEDLINE | ID: mdl-32074750

RESUMO

Objective: To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Methods: Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. Results: A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion: CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Hipofaríngeas/tratamento farmacológico , Quimioterapia de Indução , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Humanos , Receptores de Hialuronatos/genética , Neoplasias Hipofaríngeas/genética , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-6/genética
5.
N Engl J Med ; 382(7): 622-631, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053298

RESUMO

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glucocorticoides/administração & dosagem , Falência Renal Crônica/prevenção & controle , Troca Plasmática , Administração Oral , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Terapia Combinada , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Incidência , Quimioterapia de Indução , Nefropatias/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Rituximab/uso terapêutico
6.
Ann Hematol ; 99(3): 519-525, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970449

RESUMO

One hundred and eight consecutive acute myeloid leukemia (AML) patients aged 60 or less treated with two different induction regimens were retrospectively analyzed. Induction regimen for the first 50 consecutive patients was DA3+7, and the following 58 patients received cladribine 5 mg/m2 on days 1 through 5 in addition to DA3+7 (DAC). There were no significant differences in the median age and the proportion of patients with unfavorable characteristics between the two groups. Remission after induction chemotherapy was achieved in 30/50 (60%) patients in DA3+7 and in 46/58 (79%) in DAC group (p = 0.028). The median survival in the DA3+7 group was 18 months, while in the DAC group it was not reached (p = 0.034). We confirmed results from other research groups by demonstrating improved remission induction rate and overall survival of AML patients aged 60 years or less treated with DAC induction compared with standard DA3+7 induction chemotherapy.


Assuntos
Cladribina/administração & dosagem , Quimioterapia de Indução , Leucemia Mieloide Aguda , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
7.
Medicine (Baltimore) ; 99(1): e18574, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895802

RESUMO

Progranulin (PGRN) is a secreted protein that can regulate cell cycle progression, cell motility, and tumorigenesis. The PGRN expression in hematological malignancies is limited to multiple myeloma, but its expression and survival prognostic role in acute myeloid leukemia (AML) is still controversial.To evaluate the PGRN expression and estimate its survival prognostic role in AML patients.In this study, all patients were divided into three groups, which included 38 newly diagnosed adult AML patients, 33 complete remissions (CR-AML) patients, and 60 healthy control (HC) patients. The endpoints were relapse-free survival (RFS) and overall survival (OS). We investigated plasma PGRN levels by using enzyme-linked immunosorbent assay.Plasma PGRN levels in AML patients were higher than that in CR-AML and HC groups. After two chemo cycles, 16 patients had complete remission (CR). The level of plasma PGRN in non-CR patients compared to CR patients was obviously different (median 44.19 vs 21.10 ng/mL) (P = .025). In non-M3 (French-American-British classification) patients, 70% (21/30) patients relapsed in 1 year and 80% (24/80) patients died in the observed time. Using the value (median 19.95) as a "cut-off" value, we have divided non-M3 patients into low- and high-PGRN expression groups. High-PGRN expression patients had a poorer RFS with a median of 5.4 months (95% CI 3.7-7.1) and low-PGRN expression patients had a good RFS with a median of 8.9 months (95% CI 6.3-11.5; P = .027). In the survival analyses, high-PGRN expression of AML patients had shorter OS than low-PGRN expression of AML patients (6.2 vs 20.5 months, P = .008).PGRN is overexpressed in AML, which is a convenient and independent prognostic marker that is measured easily in AML patients.


Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Progranulinas/sangue , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto Jovem
8.
J Cancer Res Clin Oncol ; 146(3): 749-759, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31788741

RESUMO

PURPOSE: The German Maintenance Study (GERMAIN) was designed to evaluate the impact of lenalidomide maintenance after induction therapy with bortezomib, melphalan and prednisolone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (MM) patients. METHODS: Due to poor accrual and high dropout rate, only 85 patients (planned 286) entered the trial and 40 (planned 200) were randomized to lenalidomide maintenance (n = 19) vs. observation (n = 21). RESULTS: The primary endpoint, improved progression-free survival, was not met (p = 0.3572). After a median follow-up of 12.9 months, median progression-free survival in the lenalidomide arm was 14.4 months and 11.4 months with placebo. The hazard ratio 0.621 (95% confidence interval: [0.224, 1.725]) was about the same as expected (0.625). However, with only 40 patients randomized, the actual power to detect a difference was 11%. Of patients receiving at least one dose of induction, 54% were frail according to a modified International Myeloma Working Group frailty score. Discontinuations were high during induction (47%), and affected mainly frail patients (54%). Despite a higher rate of adverse events in the lenalidomide arm (p = 0.0061), only 2 patients discontinued lenalidomide due to toxicity. CONCLUSION: A frailty assessment with appropriate dose modification for induction therapy should be mandatory for all elderly non-transplant-eligible myeloma patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fragilidade , Quimioterapia de Indução/métodos , Lenalidomida/uso terapêutico , Quimioterapia de Manutenção/métodos , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bortezomib/uso terapêutico , Método Duplo-Cego , Feminino , Idoso Fragilizado , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Melfalan/uso terapêutico , Mieloma Múltiplo/mortalidade , Prednisolona/uso terapêutico , Intervalo Livre de Progressão
9.
Hematol Oncol ; 38(1): 74-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31755141

RESUMO

High levels of acute phase reactants can be associated with adverse outcome in patients with various solid tumor types. For patients with acute myeloid leukemia (AML), this correlation is unknown. We retrospectively investigated the prognostic value of pretreatment acute phase protein levels in 282 consecutive newly diagnosed AML patients undergoing at least one cycle of intensive induction chemotherapy. We applied a new score integrating pre-treatment C-reactive protein (CRP), fibrinogen, and albumin levels termed the CFA ratio, and we stratified patients into two groups: Patients with a CFA ratio below 3.06 had decisively better progression-free (26.2 vs 7.7 months; P < .001), disease-free (56.4 vs 8.7 months; P < .001), and overall survival (61.2 vs 13.8 months; P < .001). Results remained significant when adjusting for confounders including European Leukemia Network risk group. Early mortality also tended to be lower in the low CFA ratio group. Finally, patients with lower modified Glasgow prognostic score (mGPS) similarly had better outcome. In conclusion, our data suggest that an elevated CFA ratio as well as a high mGPS are associated with adverse outcome in patients with newly diagnosed AML undergoing intensive induction. These parameters should undergo prospective evaluation for their contribution to risk profiling in AML patients.


Assuntos
Proteínas da Fase Aguda/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Transplante de Células-Tronco Hematopoéticas/mortalidade , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/mortalidade , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Adulto Jovem
10.
Lancet Haematol ; 7(2): e122-e133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837959

RESUMO

BACKGROUND: Increased aurora A kinase (AAK) expression occurs in acute myeloid leukaemia; AAK inhibition is a promising therapeutic target in this disease. We therefore aimed to assess the activity of alisertib combined with 7 + 3 induction chemotherapy in previously untreated patients with high-risk acute myeloid leukaemia. METHODS: We did a single-arm, phase 2 trial of patients recruited from the Dana-Farber/Harvard Cancer Center in the USA. Eligible patients had previously untreated acute myeloid leukaemia, an Eastern Cooperative Oncology Group performance status of 0-2, and were at high risk of disease as defined by the presence of an adverse-risk karyotype, the presence of secondary acute myeloid leukaemia arising from previous myelodysplastic syndrome or myeloproliferative neoplasm, the presence of therapy-related acute myeloid leukaemia, or being 65 years or older. Enrolled patients received 7 + 3 induction chemotherapy of continuous infusion of cytarabine (100 mg/m2 per day on days 1-7) and intravenous bolus of idarubicin (12 mg/m2 per day on days 1-3). Oral alisertib (30 mg) was given twice per day on days 8-15. Patients could receive up to four consolidation cycles with cytarabine and alisertib, and alisertib maintenance for 12 months. The primary endpoint was a composite including the proportion of patients achieving complete remission and those with a complete remission with incomplete neutrophil or platelet count recovery. Analyses were per-protocol. This study is registered with Clinicaltrials.gov, number NCT02560025, and has completed enrolment. FINDINGS: Between Dec 31, 2015, and Aug 1, 2017, we enrolled a total of 39 eligible patients. 19 (49%) of 39 patients had secondary acute myeloid leukaemia and three (8%) had therapy-related acute myeloid leukaemia. At mid-induction, 33 (85%) of 39 patients showed marrow aplasia, six (15%) received re-induction. The median follow-up was 13·7 months (IQR 12·7-14·4). Composite remission was 64% (two-stage 95% CI 48-79), with 20 (51%) of 39 patients achieving complete remission and five (13%) achieving complete remission with incomplete neutrophil or platelet count recovery. The most common grade 3 or 4 adverse events included febrile neutropenia (16 [41%] of 39), neutropenia (12 [31%]), thrombocytopenia (13 [33%]), anaemia (11 [28%]), anorexia (nine [23%]), and oral mucositis (four [10%]). No treatment-related deaths were observed. INTERPRETATION: These results suggest that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. This study met criteria to move forward to a future randomised trial. FUNDING: Millennium Pharmaceuticals.


Assuntos
Azepinas/administração & dosagem , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Pirimidinas/administração & dosagem , Idoso , Azepinas/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Fatores de Risco
11.
J Oncol Pharm Pract ; 26(1): 200-205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30760167

RESUMO

Relapsed/refractory acute lymphoblastic leukemia poses a significant clinical challenge due to its poor prognosis, with survival rates of less than a year, even with novel therapies. Patients frequently experience toxicities from induction chemotherapy such as hepatotoxicity, which can limit therapeutic options upon relapse. Blinatumomab, a novel immunotherapy, has demonstrated excellent efficacy in relapsed/refractory acute lymphoblastic leukemia; however, there are limited data on use of this agent in patients with significant organ dysfunction. In this report, we describe the safe and effective use of blinatumomab in an adult patient with refractory Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia in the setting of severe hepatic dysfunction. Blinatumomab may represent a viable option to treat relapsed/refractory acute lymphoblastic leukemia in patients with significant hepatic dysfunction.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Idoso , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia
12.
Support Care Cancer ; 28(1): 73-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30980260

RESUMO

BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Náusea/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Vômito/diagnóstico , Adulto , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Resultado do Tratamento , Vômito/induzido quimicamente
13.
Eur Radiol ; 30(1): 537-546, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31372781

RESUMO

OBJECTIVES: To establish and validate a radiomics nomogram for prediction of induction chemotherapy (IC) response and survival in nasopharyngeal carcinoma (NPC) patients. METHODS: One hundred twenty-three NPC patients (100 in training and 23 in validation cohort) with multi-MR images were enrolled. A radiomics nomogram was established by integrating the clinical data and radiomics signature generated by support vector machine. RESULTS: The radiomics signature consisting of 19 selected features from the joint T1-weighted (T1-WI), T2-weighted (T2-WI), and contrast-enhanced T1-weighted MRI images (T1-C) showed good prognostic performance in terms of evaluating IC response in two cohorts. The radiomics nomogram established by integrating the radiomics signature with clinical data outperformed clinical nomogram alone (C-index in validation cohort, 0.863 vs 0.549; p < 0.01). Decision curve analysis demonstrated the clinical utility of the radiomics nomogram. Survival analysis showed that IC responders had significant better PFS (progression-free survival) than non-responders (3-year PFS 84.81% vs 39.75%, p < 0.001). Low-risk groups defined by radiomics signature had significant better PFS than high-risk groups (3-year PFS 76.24% vs 48.04%, p < 0.05). CONCLUSIONS: Multiparametric MRI-based radiomics could be helpful for personalized risk stratification and treatment in NPC patients receiving IC. KEY POINTS: • MRI Radiomics can predict IC response and survival in non-endemic NPC. • Radiomics signature in combination with clinical data showed excellent predictive performance. • Radiomics signature could separate patients into two groups with different prognosis.


Assuntos
Quimioterapia de Indução/métodos , Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Nomogramas , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Máquina de Vetores de Suporte , Análise de Sobrevida , Resultado do Tratamento
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1754-1760, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839034

RESUMO

OBJECTIVE: To investigate the clinical biological characteristics of children with Ph+ ALL and the factors that affecting its prognostic. METHODS: 34 children with Ph+ ALL were selected retrospectively in the period from January 2006 to December 2017; the clinical biological characteristics, clinical efficacy for short-term and survival time for long-term were recorded and the related factors that affecting the clinical efficacy for short-term and survival time for long-term were evaluated. RESULTS: The median overall survival time was 16.5 months and the cumulative OS rates for 2 years and 5 years with followed-up were separately (61.57±7.09)%, (50.75±8.22)%. The median progression-free survival time was 13.5 months and the cumulative progression-free survival rates for 2 years and 5 years with followed-up were separately (54.49±6.77)%, (48.77±7.42)%. The early treatment response of patients with myeloid antigen expression were significantly lower than the patients without myeloid antigen expression (P<0.05). The CR rate in one treatment course of patients with good response for early treatment response group were significantly higher than the patients with poor response for early treatment response (P<0.05). The CR rate in one treatment course of the patients with TKI addition in induction therapy period group were significantly higher than the patients with chemotherapy used alone(P<0.05). The OS rate and PFS rate of patients in chemotherapy + TKI + allo-HSCT and chemotherapy + TKI group were significantly higher than the patients with chemotherapy used alone group(P<0.05). Univariate analysis showed that the factors affecting OS rate of children with Ph+ ALL for 2 years with followed-up included baseline WBC count level, LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P<0.05) and the factors that the affecting PFS rate of children with Ph+ ALL for 2 years with followed-up included LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P<0.05). Multivariate analysis showed that the distances between lower splenic margin and costal margin 3 cm were independent risk factors on OS rate and PFS rate of children with Ph+ ALL (P<0.05). CONCLUSION: Children with Ph+ ALL possess unique clinical and biological features. The prognosis of patients with chemotherapy used alone is more poor, and the combination of chemotherapy and TKI can effectively increase the survival benefit; patients with Ph+ ALL combined with myeloid antigen (+) shows a poor early treatment response. while the distances between lower splenic margin and costal margin 3 cm are independent risk factors on clinical prognosis of children with Ph (+) ALL.


Assuntos
Quimioterapia de Indução , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Proteínas de Fusão bcr-abl , Humanos , Prognóstico , Indução de Remissão , Estudos Retrospectivos
17.
Medicina (B Aires) ; 79(Spec 6/1): 576-581, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31864229

RESUMO

Locally advanced pancreatic cancer (LAPC) has several definitions, but it is essentially a non-metastatic tumor, in which the initial surgical resection is not considered beneficial due to the extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of chemotherapy with calcium leucovorin, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and gemcitabine-nab (nanoparticle albumin-bound)-paclitaxel (gem-nab) had very important implications for the management of patients with LAPC. After 4 to 6 months of induction chemotherapy, a large proportion of them have stable disease or even tumor regression, allowing to rescue those who initially were not candidates for surgery, with 30-35 months overall survival after surgery.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Desoxicitidina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Análise de Sobrevida
18.
Medicine (Baltimore) ; 98(51): e18484, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861031

RESUMO

Although induction chemotherapy (IC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) is the new standard treatment option in locoregionally advanced nasopharyngeal carcinoma (NPC), many patients fail to receive CC. The aim of this study was to investigate long-term survival outcomes and toxicities in these patients who are treated with IC before IMRT without CC.We retrospectively reviewed 332 untreated, newly diagnosed locoregionally advanced NPC patients who received IC before IMRT alone at our institution from May 2008 through April 2014. The IC was administered every 3 weeks for 1 to 4 cycles. Acute and late radiation-related toxicities were graded according to the acute and late radiation morbidity scoring criteria of the radiation therapy oncology group. The accumulated survival was calculated according to the Kaplan-Meier method. The log-rank test was used to compare the difference in survival.With a median follow-up duration of 65 months (range: 8-110 months), the 5-year estimated locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates were 93.4%, 91.7%, 85.8%, and 82.5%, respectively. Older age and advanced T stage were adverse prognostic factors for overall survival, and the absence of comorbidity was a favorable prognostic factor for PFS. However, acceptable acute complications were observed in these patients.IC combined with IMRT alone provides promising long-term survival outcomes with manageable toxicities. Therefore, the omission of CC from the standard treatment did not affect survival outcomes.


Assuntos
Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
19.
Acta otorrinolaringol. esp ; 70(6): 315-326, nov.-dic. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-184876

RESUMO

Introducción y objetivos: El tratamiento de los pacientes con carcinoma de hipofaringe localmente avanzado incluye la cirugía o combinaciones de radioterapia y quimioterapia realizadas en el contexto de protocolos de preservación de órgano. El objetivo del presente estudio es analizar los resultados obtenidos en pacientes con tumores localmente avanzados de hipofaringe tratados en un centro a lo largo de un periodo de 30 años. Métodos: Estudio retrospectivo de 278 pacientes con tumores de hipofaringe T3-T4 tratados durante el periodo 1985-2015 en un hospital terciario. Resultados: Un 15,5% de los pacientes recibieron tratamiento paliativo, un 38,1% cirugía, habitualmente con radioterapia o quimiorradioterapia postoperatoria, y un 46,4% radioterapia o quimiorradioterapia. La supervivencia específica a los 5 años fue del 39,7% (IC 95% 33,7-45,7). La cirugía consiguió un mejor control local de la enfermedad, si bien este mejor control local no se vio reflejado en una mejoría de la supervivencia específica para los pacientes con tumores T3. La supervivencia a los 5 años libre de disfunción laríngea para los pacientes tratados de forma conservadora fue del 36,4%. De acuerdo con los resultados de un análisis multivariante, las variables que se relacionaron con un empeoramiento de la supervivencia específica fueron la categoría de extensión local T4, de extensión regional N2-N3 y la localización del tumor en la pared posterior de la hipofaringe. Conclusiones: No aparecieron diferencias significativas en función del tipo de tratamiento para los pacientes con tumores de hipofaringe T3. Para los pacientes con tumores T4 la cirugía consiguió un incremento significativo de la supervivencia


Introduction and objectives: The treatment of locally advanced carcinomas of the hypopharynx may include surgery or several combinations of radiotherapy and chemotherapy as organ preservation strategies. The objective of the present study is to analyze the results of locally advanced hypopharyngeal carcinoma patients treated in a single centre over a 30-year period. Methods: Retrospective chart review of 278 patients with T3-T4 hypopharyngeal carcinomas treated between 1985 and 2015 at a tertiary institution. Results: As much as 15.5% of the patients received only palliative treatment. Surgery, usually followed by radiotherapy or chemoradiotherapy was offered to 38.1% of the patients, and radiotherapy or chemoradiotherapy alone was offered to the remaining 46.6% of the patients. Cause-specific survival at 5 years was 39.7% (95% CI 33.7-45.7) for the whole sample. Surgery achieved better local control of the disease, but these figures did not translate into an increase of cause-specific survival for T3 tumours. Five-year survival free of laryngeal dysfunction for patients who received conservative treatment was 36.4%. In a multivariate analysis, only T4 local extension, N2-3 category, and posterior hypopharyngeal wall location related significantly with cause-specific survival. Conclusions: There were no significant differences in cause-specific survival related to treatment modality for T3 carcinomas. On the other hand, surgery achieved a significant increase in cause-specific survival for T4 hypopharyngeal carcinomas


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma/epidemiologia , Neoplasias Hipofaríngeas/epidemiologia , Neoplasias Hipofaríngeas/terapia , Carcinoma/terapia , Estudos Retrospectivos , Hipofaringe/patologia , Quimiorradioterapia/tendências , Quimioterapia de Indução , Protocolos de Quimioterapia Combinada Antineoplásica
20.
Medicine (Baltimore) ; 98(44): e17794, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689856

RESUMO

RATIONALE: Bing-Neel syndrome (BNS) is a rare manifestation of Waldenström macroglobulinemia (WM) with <200 cases reported in the literature. Herein, we describe a case of newly diagnosed BNS treated with a novel therapeutic strategy. PATIENT CONCERNS: A 67-year-old woman diagnosed with asymptomatic WM 3 years ago presented with gradual vision deterioration the past 3 months. Ophthalmologic examination revealed bilateral reduction in visual acuity (7/10) and bilateral optic disc swelling which was more prominent in the left eye. DIAGNOSES: Brain imaging revealed bilateral swelling of optic nerves extending from the retina to the optic chiasm and swelling of the left optic tract. Patchy enhancement of optic nerves was also shown upon intravenous contrast administration. Flow cytometry of the cerebrospinal fluid (CSF) revealed the presence of κ-light chain restricted, monoclonal B-lymphocytes. CSF protein electrophoresis showed a monoclonal band in the gamma region and immunofixation was positive for immunoglobulin M and kappa light chain. Thus, the diagnosis of BNS was established. INTERVENTIONS: The patient was initially treated with intrathecal methotrexate and systemic chemotherapy. Following 2 intrathecal methotrexate infusions, CSF flow cytometry did not detect any cells, whereas the patient reported improvement in visual acuity. Therefore, we opted to start maintenance treatment with IV rituximab and per os ibrutinib. OUTCOMES: Following 1 year posttreatment initiation, visual problems have resolved completely and the patient remains on hematologic and imaging complete response. LESSONS: We propose a novel sequential chemoimmunotherapy approach for BNS treatment aiming both at rapid disease control and deep and durable remission with minimization of induced toxicity.


Assuntos
Encefalopatias/tratamento farmacológico , Imunoterapia/métodos , Quimioterapia de Indução/métodos , Neurite Óptica/tratamento farmacológico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Idoso , Encefalopatias/imunologia , Feminino , Humanos , Neurite Óptica/imunologia , Síndrome , Macroglobulinemia de Waldenstrom/imunologia
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