Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 309
Filtrar
1.
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
3.
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
4.
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
5.
Pediatr Blood Cancer ; 67(1): e28025, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571345

RESUMO

Minimal residual disease (MRD) analysis has become a powerful indicator to refine therapy in acute lymphoblastic leukemia (ALL). Here, we present an MRD detection based on the next-generation sequencing of PTEN exon 7 mutations (NGS-PTEN) in 30 pediatric T-cell ALL patients. By comparing the NGS-PTEN results with current quantitative PCR of antigen receptor gene rearrangements (qPCR-Ig/TR), an overall concordance of 80% was found between the two methods. However, the NGS-PTEN qualified a lower number of high-risk patients than qPCR-Ig/TR. These findings suggest that NGS-PTEN is a promising tool that could potentially be used to support current MRD methodologies for T-ALL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Quimioterapia de Indução/efeitos adversos , Mutação , Neoplasia Residual/diagnóstico , PTEN Fosfo-Hidrolase/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasia Residual/induzido quimicamente , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico
6.
Radiat Oncol ; 14(1): 229, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842910

RESUMO

OBJECTIVES: To observe the risk factors affecting the occurrence of RP after gemcitabine-based induction chemotherapy. METHODS: Between January 2010 and December 2017, patients with NSCLC received gemcitabine or docetaxel chemotherapy, followed by radiotherapy at Zhejiang cancer hospital were enrolled in this study. Patients were treated with gemcitabine or docetaxel induction chemotherapy, followed by radiotherapy or concurrent chemoradiotherapy. Acute radiation pneumonitis was scored post chemoradiotherapy. RESULTS: One hundred and eighty-four patients with NSCLC were included in the gemcitabine group and 144 in the docetaxel group. The gemcitabine group experienced a higher incidence of grade ≥ 2 RP, compared with docetaxel group (25.5% Vs. 13.2%, P = 0.005). The optimal cutoff values of lung V5, V20, V30 and MLD were set at 44% (AUC [area under the curve] = 0.593), 24% (AUC = 0.607), 14.2% (AUC = 0.622) and 1226 cGy (AUC = 0.626). On multivariate analysis, only lung V30 was identified as a predictor for grade ≥ 2 RP (P = 0.03). The grade ≥ 2 RP rate was only 9.4% for the low-risk group (Lung V5 ≤ 44%, V20 ≤ 24%, V30 ≤ 14.2%, and MLD ≤ 1226 cGy) in patients received gemcitabine induction chemotherapy. CONCLUSIONS: Gemcitabine chemotherapy before thoracic radiotherapy in NSCLC patients was related to a higher incidence of grade ≥ 2 RP, compared with docetaxel chemotherapy. The Lung dose-volume variable V30 was the best predictor of grade ≥ 2 RP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/diagnóstico , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
7.
Indian J Cancer ; 56(4): 320-324, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607700

RESUMO

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH. RESULTS: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114-129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059). CONCLUSION: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Síndrome de Secreção Inadequada de HAD/epidemiologia , Quimioterapia de Indução/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Vincristina/efeitos adversos , Adolescente , Antineoplásicos Fitogênicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Hiponatremia , Síndrome de Secreção Inadequada de HAD/etiologia , Incidência , Índia/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Estudos Prospectivos , Centros de Atenção Terciária , Vincristina/uso terapêutico
8.
Anticancer Res ; 39(8): 4305-4314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366522

RESUMO

BACKGROUND/AIM: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. PATIENTS AND METHODS: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. RESULTS: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. CONCLUSION: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Náusea/epidemiologia , Vômito/epidemiologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Fatores de Risco , Vômito/induzido quimicamente , Vômito/patologia
9.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373469

RESUMO

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Lesão Renal Aguda/terapia , Adulto , Dexametasona/uso terapêutico , Edema/induzido quimicamente , Febre de Causa Desconhecida/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Quimioterapia de Indução/efeitos adversos , Masculino , Diálise Renal , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome
10.
Ann Transplant ; 24: 412-417, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296835

RESUMO

BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.


Assuntos
Infecções por Citomegalovirus/etiologia , Imunossupressores/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adulto , Vírus BK , Citomegalovirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Zhonghua Xue Ye Xue Za Zhi ; 40(6): 497-501, 2019 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-31340623

RESUMO

Objective: To compare the time of the recovery of neutrophils or leukocytes by pegylated recombinant human granulocyte stimulating factor (PEG-rhG-CSF) or common recombinant human granulocyte stimulating factor (rhG-CSF) in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients. At the same time, the incidences of infection and hospitalization were compared. Methods: A prospective randomized controlled trial was conducted in patients with newly diagnosed AML who met the enrollment criteria from August 2014 to December 2017. The patients were randomly divided into two groups according to a 1:1 ratio: PEG-rhG-CSF group and rhG-CSF group. The time of neutrophil or leukocyte recovery, infection rate and hospitalization interval were compared between the two groups. Results: 60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. There were no significant differences in age, chemotherapy regimen, pre-chemotherapy ANC, WBC, and induction efficacy between the two groups (P>0.05) . The median time (range) of ANC or WBC recovery in patients with PEG-rhG-CSF and rhG-CSF were 19 (14-35) d and 19 (15-26) d, respectively, with no statistical difference (P=0.566) . The incidences of infection in the PEG-rhG-CSF group and the rhG-CSF group were 90.0%and 93.3%, respectively, and there was no statistical difference (P=1.000) . The median days of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, respectively, with no statistical difference (P=0.530) . Conclusions: In AML patients after induction therapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in ANC or WBC recovery time, infection incidence and hospitalization time.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide Aguda , Neutropenia , Humanos , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Neutrófilos , Estudos Prospectivos , Proteínas Recombinantes
12.
Support Care Cancer ; 27(9): 3613-3622, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31165931

RESUMO

BACKGROUND: Invasive fungal infection (IFI) causes high morbidity and mortality during acute myeloid leukemia (AML) treatment. Interventions to prevent fungal infection, including air filtration systems and antifungal prophylaxis, may improve outcomes in this group of patients. However, they are expensive and therefore inapplicable in resource-limited countries. The benefit of antifungal therapy is also dependent on the local epidemiology. That led us to conduct the study to evaluate the characteristics and impact of IFI in AML patients without prophylaxis in our setting. METHODS: Clinical data from patients with AML who have been treated with chemotherapy without antifungal prophylaxis were retrieved during a 5-year period at Thailand's hematology referral center. Incidence and risk factors of IFI and outcomes of patients were evaluated. RESULTS: Among 292 chemotherapy courses, there were 65 (22.3%) episodes of IFI. Of those, 10 (15.4%) were proven, 19 (29.2%) were probable, and 36 (55.4%) were categorized as being possible IFI. Molds were the most commonly observed causative pathogens (93.1%). The incidence of probable/proven IFI was highest during first induction (20.5%), followed by second induction (6.1%), and consolidation (2.7%). A long duration of neutropenia, old age, and low serum albumin were the strongest predictors of IFI. Compared with patients who had no IFI, patients with probable/proven IFI had a longer length of hospital stay and higher in-hospital mortality. Patients with proven IFI had a significantly worse outcome at 1 year. CONCLUSIONS: These results suggest the change in health policy to implement IFI preventive measures to improve outcomes of AML treatment.


Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas , Profilaxia Pré-Exposição/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Recursos em Saúde , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Tempo de Internação , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neutropenia/patologia , Fatores de Risco , Tailândia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Anticancer Res ; 39(6): 3059-3065, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177149

RESUMO

BACKGROUND: Induction chemotherapy (IC) for head and neck cancer (HNC) often causes severe side-effects. However, it has still been challenging to predict the adverse events. The present study aimed to evaluate the role of hematological inflammatory markers in predicting severe side-effects caused by IC. MATERIALS AND METHODS: A total of 54 HNC patients who underwent IC were enrolled. The association between severe side-effects and pre-treatment hematological inflammatory markers [the C-reactive protein (CRP) to albumin ratio (CAR), the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR)] were evaluated. RESULTS: In the univariate analysis, the incidence of whole severe side-effects (grade 4), febrile neutropenia (above grade 3), and hyponatremia (above grade 3) were significantly higher in the high CAR and high GPS groups. Multivariate analysis revealed that high CAR and mGPS were independent predictors of these side-effects. CONCLUSION: CAR and mGPS were significant predictors of severe side-effects. These data can potentially offer patients an improved quality of life during cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimioterapia de Indução/efeitos adversos , Mediadores da Inflamação/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Neutropenia Febril Induzida por Quimioterapia/sangue , Neutropenia Febril Induzida por Quimioterapia/diagnóstico , Cisplatino/efeitos adversos , Docetaxel/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Hiponatremia/sangue , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Incidência , Japão/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Fatores de Tempo , Resultado do Tratamento
14.
N Engl J Med ; 381(12): 1124-1135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31150573

RESUMO

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem
15.
BMJ Case Rep ; 12(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31101747

RESUMO

Anthracyclines are an effective chemotherapy agent. However, very few cases of idarubicin-induced cardiomyopathy exist. Herein, we describe a case of first-dose idarubicin-related acute heart failure in a woman with a history of myelodysplastic syndrome converted to acute myeloid leukaemia.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Idarubicina/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Antibióticos Antineoplásicos/administração & dosagem , Evolução Fatal , Feminino , Humanos , Idarubicina/administração & dosagem , Quimioterapia de Indução/efeitos adversos
16.
Pediatr Blood Cancer ; 66(9): e27834, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31131954

RESUMO

Mucormycosis in pediatric oncology patients is a rare invasive fungal infection associated with significant morbidity and mortality. We describe five patients diagnosed with mucormycosis during induction chemotherapy for acute lymphoblastic leukemia at our institution. All of the patients in our series survived, some in spite of having disseminated disease. Most of the patients' chemotherapy was modified with the aim of controlling their leukemia while minimizing immunosuppression until their fungal infection was under control. Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach can lead to excellent outcomes, even in patients undergoing intensive chemotherapy.


Assuntos
Quimioterapia de Indução/efeitos adversos , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mucormicose/induzido quimicamente , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Estudos Retrospectivos
17.
Int J Radiat Oncol Biol Phys ; 104(4): 836-844, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30954521

RESUMO

PURPOSE: To evaluate the long-term locoregional control, failure patterns, and late toxicity after reducing the target volume and radiation dose in patients with locoregionally advanced nasopharyngeal carcinoma patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Previously untreated patients with locoregionally advanced nasopharyngeal carcinoma were recruited into this prospective study. All patients received 2 cycles of IC followed by CCRT. The gross tumor volumes of the nasopharynx (GTVnx) and the neck lymph nodes (GTVnd) were delineated according to the post-IC tumor extension and received full therapeutic doses (68 Gy and 62-66 Gy, respectively). The primary tumor shrinkage after IC was included in the high-risk clinical target volume (CTV1) with a reduced dose of 60 Gy. The locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. RESULTS: There were 112 patients enrolled in this study. The average mean dose of post-GTVnx, post-GTVnd (left), post-GTVnd (right), post-CTV1, and post-low-risk clinical target volume (CTV2) was 75.24, 68.97, 69.16, 70.49, and 63.37 Gy, respectively. With a median follow-up of 125.95 months, the 10-year LRRFS, DMFS and OS were 89.0%, 83.3%, and 75.9%, respectively. There were 8 local recurrences and 6 regional recurrences in 12 patients. All 8 of the local recurrences were in-field; among the 6 regional recurrences, 4 were in-field, 1 was marginal, and 1 was out-field. The most common late toxicities were grade 1 to 2 subcutaneous fibrosis, hearing loss, and xerostomia. No grade 4 late toxicities were observed. CONCLUSIONS: Reduction of the target volumes according to the post-IC tumor extension and radiation dose to the post-IC tumor shrinkage could yield excellent long-term locoregional control with limited marginal and out-field recurrences and mild late toxicities.


Assuntos
Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Tamanho da Amostra , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
18.
BMC Cancer ; 19(1): 358, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30991992

RESUMO

BACKGROUND: Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML). METHODS: Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity ( Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy. RESULTS: The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1-68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety. CONCLUSIONS: Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML. TRIAL REGISTRATION: Clinicaltrials.gov NCT02440178, registered May 12th 2015.


Assuntos
Antifúngicos/uso terapêutico , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/complicações , Micafungina/uso terapêutico , Micoses/etiologia , Micoses/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Resultado do Tratamento , Adulto Jovem
19.
BMC Cancer ; 19(1): 287, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925912

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system (CNS) with rising incidence among patients > 65 years. Although elderly patients are able to tolerate aggressive systemic chemotherapy, previous studies have demonstrated inferior outcomes for patients who present with a poor performance status (PS) and older age. Usually, intensive treatment approaches including high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) are only offered to patients younger than 65-70 years of age. METHODS: This is an open-label, multicentric, non-randomized, single arm phase II trial. We will recruit 51 immuno-competent patients with newly diagnosed PCNSL from 12 German centers. The objective is to investigate the efficacy of age-adapted induction treatment followed by HDT-ASCT. All enrolled patients will undergo induction chemotherapy consisting of 2 cycles of rituximab 375 mg/m2/d (days 0 & 4), methotrexate 3.5 g/m2 (d1), and cytarabine 2 × 2 g/m2/d (d2-3) every 21 days. After 2 cycles of induction chemotherapy, patients achieving at least stable disease will undergo HDT-ASCT with busulfan 3.2 mg/kg/d (days - 7-(- 6)) and thiotepa 5 mg/kg/d (days - 5-(- 4)) followed by autologous stem cell transplantation. The primary endpoint of this study is 1-year progression-free survival (PFS). Secondary endpoints include PFS, overall survival, treatment response and treatment-related morbidities. Minimal follow-up after treatment completion is 12 months. DISCUSSION: Current treatment options for PCNSL have improved over the last years, resulting in the potential to achieve durable remission or cure in patients < 70 years. Age alone may not be the only criterion to select patients for this effective treatment approach and probably many elderly patients are undertreated just because of advanced age. There have been no multicentre trials investigating this curative treatment concept in elderly and fit PCNSL patients so far. We aim to answer whether HDT-ASCT is feasible and effective in fit patients > 65 years with newly-diagnosed PCNSL. TRIAL REGISTRATION: German clinical trials registry DRKS00011932 registered 18 August 2017.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Transplante Autólogo/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos Antineoplásicos , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada/efeitos adversos , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/terapia , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Intervalo Livre de Progressão , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Tiotepa/efeitos adversos , Tiotepa/uso terapêutico
20.
Support Care Cancer ; 27(10): 3905-3912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30770977

RESUMO

PURPOSE: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors. METHODS: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (< 65 n = 260 versus ≥ 65 n = 165) using parametric and nonparametric tests. RESULTS: Among 425 cancer survivors with CIPN, mean age was 60.9 (SD 10.5). CIPN location did not differ by age (overall 68% hands and feet, 27% only feet, 5% only hands). For patient-reported measures, older survivors reported less severe pain in the hands and feet than younger survivors. In addition, older survivors reported lower interference with general activity, routine activities, normal work, enjoyment of life, sleep, mood, relations with other people, and sexual activity. No age differences in sensory and motor symptom scores were found. In contrast, for objective measures, older survivors had worse light touch and cold sensations in their feet and worse vibration detection in their hands and feet. CONCLUSIONS: Despite having worse light touch, cold, and vibration sensations, older cancer survivors with CIPN reported less severe pain and interference with activities. This discordance highlights the importance of including both patient-reported and objective measures to assess CIPN in cancer survivors to better evaluate this clinical condition.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer/estatística & dados numéricos , Dor/diagnóstico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Autorrelato/estatística & dados numéricos , Idoso , Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Platina/efeitos adversos , Platina/uso terapêutico , Inquéritos e Questionários , Taxoides/efeitos adversos , Taxoides/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA