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1.
Medicine (Baltimore) ; 98(38): e17262, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568001

RESUMO

BACKGROUND: This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with HER2-positive breast cancer (HER2-PBC). METHODS: A comprehensive literature search for this study will consist of 2 parts: electronic database records and gray literature. The electronic database literatures are searched from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from inception up to the present. In addition, gray literatures, such as dissertations, ongoing trials, and so on, will also be searched. Two authors will independently read the records, extract data collection, and evaluate the risk of bias. RevMan V.5.3 software will be applied for statistical analysis. RESULTS: This study will summarize up-to-date evidence of PTD for patients with HER2-PBC via overall survival, complete response, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities. CONCLUSION: This study will provide efficacy and safety of PTD for HER2-PBC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Genes erbB-2 , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Feminino , Humanos , Trastuzumab/administração & dosagem , Resultado do Tratamento
2.
Anticancer Res ; 39(10): 5417-5425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570436

RESUMO

BACKGROUND/AIM: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate. MATERIALS AND METHODS: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis. RESULTS: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo. CONCLUSION: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Docetaxel/administração & dosagem , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Sirolimo/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células PC-3 , Inibidores de Proteínas Quinases/administração & dosagem , Sirolimo/administração & dosagem
3.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
4.
Cancer Radiother ; 23(6-7): 662-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473087

RESUMO

Chemoradiotherapy is now considered the standard of care for many locally advanced diseases. Cytotoxic drugs have been largely evaluated in this setting, with cisplatin and 5FU the most often used drugs. A large amount of pre-clinical studies has demonstrated the synergy between both modalities. Concomitant administration seems the more beneficial in many diseases. Emergence of new approaches, combining targeted therapies and radiotherapy (RT) is now a reality. The main example is the association of cetuximab and RT in head and neck carcinomas, even if, 14 years after the initial publication, the best way to use it is still unknown. New compounds as inhibitors of DNA-repair or immune checkpoints are under investigation and showed early promising results.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/tendências , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Reparo do DNA/efeitos dos fármacos , Docetaxel/administração & dosagem , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Terapia de Alvo Molecular/métodos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Fatores de Tempo
5.
Anticancer Res ; 39(8): 4337-4342, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366527

RESUMO

BACKGROUND: Induction therapy with docetaxel, cisplatin and fluorouracil (TPF) is a treatment option for locally advanced head and neck cancer (LAHNC), but it is not known which patients are appropriate for TPF. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with LAHNC who underwent induction TPF, and evaluated factors predictive of the completion of TPF treatment (defined as ≥3 cycles administered). RESULTS: Of the total 93 enrolled patients, 73 (78.5%) achieved therapy completion. In a multivariate analysis, hypolaryngeal/ laryngeal primary tumor site was a negative predictive factor (hazard ratio(HR)=0.32, 95% confidence interval(CI)=0.11-0.96, p=0.041) and body mass index ≥22 kg/m2 was a positive predictive factor (hazard ratio=3.51, 95% confidence intervaI=1.04-11.83, p=0.043) of TPF completion. CONCLUSION: For patients with LAHNC, oropharyngeal primary tumor site and high body mass index can be used to predict TPF completion and may contribute to decisions on the indications for TPF in terms of safety and tolerability.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia
6.
Anticancer Res ; 39(8): 4411-4414, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366538

RESUMO

BACKGROUND/AIM: Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. PATIENTS AND METHODS: This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. RESULTS: Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. CONCLUSION: Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/efeitos adversos , Resultado do Tratamento
7.
Gynecol Oncol ; 154(3): 638-650, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307664

RESUMO

OBJECTIVES: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS). METHODS: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR. RESULTS: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I2 = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I2 = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly. CONCLUSION: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS.


Assuntos
Leiomiossarcoma/terapia , Neoplasias Uterinas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Feminino , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/radioterapia , Leiomiossarcoma/cirurgia , Estudos Observacionais como Assunto , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/radioterapia , Neoplasias Uterinas/cirurgia
8.
AAPS PharmSciTech ; 20(6): 220, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201588

RESUMO

In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followed by a 3.5 times increase in the retention time in comparison with the plain drug. The single-point brain bioavailability of docetaxel was amplified by 3.3-folds, signifying a better uptake and distribution to brain employing these carriers. The findings are unique as the physically adsorbed piperine was released before the DTX, increasing the propensity of curbing the CYP3A4 enzyme, which plays a vital role in the degradation of docetaxel. Meanwhile, piperine might have compromised the P-gp efflux mechanism, which can be ascribed to the enhanced retention of the drug at the target site. The elevated target site concentrations and extended residence by a biocompatible nanocarrier supplemented with co-delivery of piperine inherit immense promises to deliver this BCS class IV drug more safely and effectively.


Assuntos
Alcaloides/química , Antineoplásicos Fitogênicos/administração & dosagem , Benzodioxóis/química , Docetaxel/administração & dosagem , Micelas , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Animais , Antineoplásicos Fitogênicos/farmacocinética , Disponibilidade Biológica , Encéfalo/metabolismo , Linhagem Celular Tumoral , Docetaxel/farmacocinética , Humanos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Med Oncol ; 36(7): 60, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31134385

RESUMO

Immune checkpoint molecules are expressed on cancer cells and regulate tumor immunity by binding to ligands on immune cells. Although soluble forms of immune checkpoint molecules have been detected in the blood of patients with some types of tumors, their roles have not been fully elucidated. Soluble PD-L1, PD-1, CD155, LAG3, and CD226 (sPD-L1, sPD-1, sCD155, sLAG3, and sCD226, respectively) were measured in the sera of 47 patients with advanced esophageal cancer and compared with those of 24 control subjects. Pretreatment levels of sPD-1 and sCD155 were significantly higher in the patients with cancer than in the control subjects (P = 0.023, P = 0.001). The sPD-1 levels tended to be higher in the patients with lymph node metastasis, a large tumor diameter, and higher levels of serum SCC antigen (P = 0.150, P = 0.189, and P = 0.078, respectively). However, higher levels of sCD155 were associated with a better response to chemotherapy and favorable overall survival (P = 0.111 and P = 0.068, respectively). After 2 courses of chemotherapy, the levels of sCD155 and sCD226 were significantly increased (P < 0.001 and P = 0.002, respectively). Moreover, the increase in sCD226 during chemotherapy was associated with poor treatment response (P = 0.019). sPD-1 levels are possibly dependent on the tumor aggressiveness of the esophageal cancer. Furthermore, the pretreatment levels of sCD155 and kinetic change of sCD226 after chemotherapy may be used as biomarkers of the treatment response and prognosis in patients with esophageal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Antígeno B7-H1/sangue , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Esofágicas/imunologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/sangue , Receptores Virais/sangue
10.
Bull Cancer ; 106(6): 527-537, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31122656

RESUMO

BACKGROUND: The aim of this investigation was to study the effects of supervised combined intermittent aerobic, muscle strength and home-based walking training programs on cardiorespiratory fitness in women with breast cancer during adjuvant chemotherapy treatment. METHODS: Thirty-two women with breast cancer undertaking adjuvant chemotherapy participated in the study (trained group n=20 and control group n=12). The trained group carried out 6weeks of supervised intermittent cycling aerobic, muscle strength and home-based walking training programs. The self-selected walking speed (WS), walking distance covered (WD), heart rate (rHR), blood lactate ([La]b) concentration and rating of perceived exertion (RPE) were assessed in the two groups during the 6-min walking test before and after the training period. RESULTS: Compared to controls, a significant increase in the WS (P<0.01) and the WD (P<0.01) accompanied by a significant decrease in resting rHR (P<0.01), exercising HR6' (P<0.01), [La]b (P<0.05), HR6'/WS (P<0.01) and [La]b/WS ratios (P<0.01) was reported in the trained group. However, a significant decrease both in WD (P<0.01) and WS (P<0.01) has been observed in the controls. No significant difference was observed in resting HR, exercising HR6', [La]b, HR6'/WS, and [La]b/WS ratios were observed in the control group. A significant improvement was observed for RPE in training group (P<0.05). However, no difference was shown in controls. CONCLUSION: Combined training based on intermittent aerobic exercise, muscle strength and walking improve cardiorespiratory responses and reduce the perception of fatigue in women with breast cancer.


Assuntos
Neoplasias da Mama/reabilitação , Aptidão Cardiorrespiratória , Exercício , Treinamento de Resistência , Caminhada , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Epirubicina/administração & dosagem , Teste de Esforço , Feminino , Fluoruracila/administração & dosagem , Frequência Cardíaca , Serviços de Assistência Domiciliar/organização & administração , Humanos , Lactatos/sangue , Pessoa de Meia-Idade , Esforço Físico , Avaliação de Programas e Projetos de Saúde
11.
J Cancer Res Clin Oncol ; 145(7): 1857-1864, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062162

RESUMO

BACKGROUND: To evaluate the value of concurrent chemotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT), we performed this retrospective cohort study to compare the efficiency and toxicities of induction chemotherapy plus IMRT alone (IC + RT) versus induction chemotherapy plus IMRT-based concurrent chemoradiotherapy (IC + CCRT). METHOD: We analyzed data from patients with locoregionally advanced NPC (stage III-IVb) who were treated at the West China hospital between January 2008 and December 2014. Patients received docetaxel, cisplatin, and 5-fluorouracil (TPF) IC followed by IMRT alone (IC + RT group) or IMRT plus cisplatin concurrent chemotherapy (IC + CCRT group). The main endpoint was overall survival (OS), which was evaluated by the Kaplan-Meier method and log-rank test. Multivariate Cox proportional hazard analysis was used to identify potential independent prognostic factors. Treatment-associated toxicities were compared between groups using the Chi squared test. RESULTS: A total of 78 patients treated with IC + RT and 76 with IC + CCRT were analyzed. The median follow-up time was 59 months (range: 7-108 months). There was no difference between patients treated with IC + RT and IC + CCRT in terms of 3-year OS (89.0% versus 88.0%, p = 0.286), progression-free survival (76.8% versus 80.0%, p = 0.142), locoregional recurrence-free survival (87.1% versus 90.5%, p = 0.156), or distant metastasis-free survival (83.6% versus 82.6%, p = 0.567). Treatment (IC + RT versus IC + CCRT) was not an independent prognostic factor for OS (HR 1.425, 95% CI 0.698-2.908; p = 0.331). IC + CCRT was associated with a higher incidence of grade 3-4 neutropenia than IC + RT during radiotherapy (11.8% versus 1.3%, p = 0.020). CONCLUSION: IC plus IMRT alone achieves similar patient survival outcomes as IC plus IMRT-based concurrent chemoradiotherapy, and has a lower incidence of toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Quimiorradioterapia , Cisplatino/administração & dosagem , Estudos de Coortes , Docetaxel/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Cancer Radiother ; 23(4): 273-280, 2019 Jul.
Artigo em Francês | MEDLINE | ID: mdl-31138520

RESUMO

PURPOSE: The objective of this study was to identify predictive factors of toxicity of docetaxel, platin, 5-fluorouracil (TPF) induction chemotherapy for locally advanced head and neck cancers. PATIENTS AND METHODS: From July 2009 to March 2015, 57 patients treated consecutively with TPF were included retrospectively. There were 47 males (83%), the median age was 56 years [40-71 years]. Thirty-eight patients (67%) were treated for inoperable cancer (highly symptomatic and/or high tumor burden) and 19 (33%) were treated for laryngeal preservation. There were 47% stage IVa, 32% stage III and 21% stage IVb. At diagnosis, there were 53% stable weight, 28% grade 1 weight loss, 17% grade 2 weight loss and 2% grade 3 weight loss. RESULTS: Forty-seven percent of patients were in partial response after TPF, 28% in complete response, 7% stable, 2% progressing and 2% discordant response. The possibility of oral feeding without a feeding tube was predictive of a better response (P=0.02). Thirty-nine percent of patients increased weight during TPF, 35% were stable, 18% in grade 1 weight loss, 6% in grade 2 and 2% in grade 3. Six of the patients (10.5%) died during chemotherapy: four from febrile neutropenia, one from pneumopathy and one of unknown cause. Age 57years and older was associated with a higher risk of grade≥3 anemia and thrombocytopenia. There was a higher risk of grade≥3 infection for weight loss at diagnosis (P=0.04) and feeding tube (P=0.05). There was a higher risk of grade≥3 neutropenia for weight loss during TPF (P=0.03). CONCLUSION: Induction chemotherapy by TPF has an strong anti-tumor efficacy (75.5% objective response) but an important morbidity with 10% toxic deaths in our very symptomatic population with a very important tumor burden. Age and nutritional status are important factors to consider.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel/efeitos adversos , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Estado Nutricional , Adulto , Fatores Etários , Idoso , Anemia/induzido quimicamente , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Nutrição Enteral , Neutropenia Febril/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Infecção/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Carga Tumoral , Perda de Peso
13.
Urologe A ; 58(9): 1066-1072, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31041460

RESUMO

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/terapia , Antagonistas de Androgênios/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Humanos , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
14.
Anticancer Res ; 39(4): 1689-1698, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952707

RESUMO

BACKGROUND/AIM: This study aimed to identify biomarkers for predicting the prognosis of advanced gastric cancer patients who received docetaxel, cisplatin, and S-1 (DCS). MATERIALS AND METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE31811). Gene-Ontology-enrichment and KEGG-pathway analysis were used for evaluating the biological functions of differentially-expressed genes. Protein-protein interaction (PPI) network and Kaplan-Meier survival analyses were employed to assess the prognostic values of hub genes. RESULTS: A total of 1,486 differentially expressed genes (DEGs) were identified, including 13 up-regulated and 1,473 down-regulated genes. KEGG pathways such as metabolic pathways, cell adhesion molecules (CAMs), PI3K-Akt signaling pathway and pathways in cancer were significantly represented. In the PPI network, the top ten hub genes ranked by degree were GNG7, PLCB1, CALML5, FGFR4, GRB2, JAK3, ADCY7, ADCY9, GNAS and KDR. Five DEGs, including ANTXR1, EFNA5, GAMT, E2F2 and NRCAM, were associated with relapse-free survival and overall survival. CONCLUSION: ANTXR1, EFNA5, GAMT, E2F2 and NRCAM are potential biomarkers and therapeutic targets for DCS treatment in GC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Cisplatino/administração & dosagem , Biologia Computacional/métodos , Docetaxel/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Tegafur/administração & dosagem , Transcriptoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Tomada de Decisão Clínica , Bases de Dados Genéticas , Docetaxel/efeitos adversos , Combinação de Medicamentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Ácido Oxônico/efeitos adversos , Medicina de Precisão , Mapas de Interação de Proteínas , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/efeitos adversos , Resultado do Tratamento
15.
Lancet ; 393(10184): 1948-1957, 2019 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-30982686

RESUMO

BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours. METHODS: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group. INTERPRETATION: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/patologia , Resultado do Tratamento
16.
Yakugaku Zasshi ; 139(4): 505-509, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30930377

RESUMO

Comprehensive identification of antigens in immune complexes (IC-antigens) is beneficial to provide insights into pathophysiology and could form the basis for novel diagnostic and treatment strategies for many immune-related diseases. Immune complexome analysis is a method for comprehensively identifying and profiling IC-antigens in biological fluids (such as serum and cerebrospinal fluid). We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases, and cancers. Fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) consists of fluorogenic derivatization of proteins, followed by HPLC of the derivatized proteins, isolation of the proteins differentially expressed in a certain group, enzymatic digestion of the isolated proteins followed by LC-tandem MS using a database-searching algorithm for protein identification. We have applied this method to understand the cardioprotective effect of pre-administration of docetaxel in adriamycin/docetaxel combination anti-cancer therapy, and the cellular processes that are affected by non-steroidal anti-inflammatory drugs (NSAIDs) in mouse stomach tissue during ulcer formation.


Assuntos
Cromatografia Líquida , Pesquisa Farmacêutica , Proteoma , Proteômica/métodos , Espectrometria de Massas em Tandem , Animais , Anti-Inflamatórios não Esteroides , Complexo Antígeno-Anticorpo , Antígenos/isolamento & purificação , Antígenos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Doenças Autoimunes/imunologia , Cardiotônicos , Docetaxel/administração & dosagem , Docetaxel/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Camundongos , Neoplasias/imunologia
17.
J Cancer Res Ther ; 15(2): 312-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964103

RESUMO

Background: A clinical study was conducted to determine the efficacy of nimotuzumab combined with docetaxel, cisplatin, and 5-fluorouracil (TPF) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) after surgery and conformal radiotherapy. Methods: Thirty-one HNSCC patients received three courses of chemotherapy every 21 days, at a dose of 75 mg/m2 of docetaxel and cisplatin on day 1 and 750 mg/m2 of 5-fluorouracil on days 1-5 followed by 200 mg/m2/week of nimotuzumab on week 1-2 (day 6-21). Results: After sequential therapy, complete and partial responses were observed in 10 (32.3%) and 17 (54.8%) patients, respectively. The overall response rate was 87.1%. A progression-free survival of 71.2% (95% confidence interval [CI] 51.6%-93.7%) and an overall survival of 78.3% (95% CI 58.9%-89.5%) were achieved at 2nd year. The most common Grade 3-4 toxicities during the complete treatment were lymphopenia (25.8%), neutropenia (22.6%), anemia (12.9%), and diarrhea (16%). In addition, no rash and treatment-related death occurred during this study. Conclusions: Nimotuzumab in combination with TPF has been well tolerated as a treatment program for locally advanced HNSCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Resultado do Tratamento
18.
Oncol Rep ; 41(6): 3335-3346, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31002355

RESUMO

Dynamic contrast enhanced­magnetic resonance imaging (DCE­MRI) contributes to the early detection and prediction of responses to chemotherapy in cancer. The aim of the present study was to investigate the feasibility of quantitative DCE­MRI parameters for noninvasively predicting the early response to DTX in epithelial ovarian cancer (EOC). In the present study, using 7,12­dimethylbenz (A) anthracene, orthotopic EOC was induced in Sprague Dawley rats. Rats with EOC were treated with docetaxel (DTX) on day 0. DCE­MRI was applied on days 0, 3, 7, 14 and 21. On day 21, the treated tumor types were categorized into sensitive and insensitive groups according to their change in size. Quantitative DCE­MRI parameters were used to assess the early response to therapy. The experiment was performed again, the treatment group was divided into sensitive and insensitive groups according to their initially obtained cut-off values, and histopathological analyses were performed. Comparing the sensitive group with the insensitive group, there were significant differences in the percentage change in the volume transfer constant (Ktrans), rate constant (kep) and initial area under the curve (IAUC) from day 3 and tumor size from day 14. During the early stages of treatment (on day 3), the percentage change of Ktrans combined with kep produced an AUC of 1, and a sensitivity and specificity of 100 and 100%, respectively, using a cut-off value of a 17.59% reduction in Ktrans and kep. From day 7, there were significant differences in the quantitative index percentage change in angiogenesis in the sensitive group compared with the insensitive group. The percentage change in Ktrans, kep and IAUC were positively correlated with the percentage of change in tumor size and angiogenesis, and negatively correlated with the percentage of change in necrosis. The results of the present study indicated that quantitative DCE­MRI parameters were superior to imaging tumor size for the early detection and prediction of the response to DTX chemotherapy in EOC.


Assuntos
Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Animais , Carcinoma Epitelial do Ovário/patologia , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Feminino , Humanos , Imagem por Ressonância Magnética , Neovascularização Patológica/patologia , Ratos , Ratos Sprague-Dawley
19.
BMC Cancer ; 19(1): 382, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023257

RESUMO

BACKGROUND: Lung cancer patients undergoing palliative chemotherapy exhibit many symptoms related to the disease, such as adverse events and infectious complications during treatment, which impacts directly their health-related quality of life (HRQOL). Nutritional status is a relevant aspect among advanced cancer patients under palliative care and food supplementation has the potential to reduce treatment-related adverse effects and improve the nutritional status. The product named AferBio® is a fermented supplement that has been described as able to provide some benefits, including the capacity to potentiate the effects of anticancer drugs, by promoting the reduction of side effects and ultimately improving HRQOL. METHODS/DESIGN: A Phase II double-blind placebo-controlled randomized clinical trial to assess the use of food supplementation with AferBio® in Stage IIIB or IV non-small cell lung cancer (NSCLC) patients beginning a second-line palliative mono-chemotherapy. The primary goal is to compare HRQOL scores between the arms of the study over time. The ten first patients included in the present study will undergo an AferBio®toxicity-testing (non-randomized phase). If no significant toxicity is found, the study will move on to the randomized phase. All patients will be randomized in blocks at a 1:1 ratio using the online tool REDCap. ECOG-PS (0-1 versus 2) criteria will be used for stratification. All patients included in the trial will be evaluated at baseline and at each chemotherapy cycle. Each evaluation will include the following: HRQOL (EORTC QLQ-C30, LC13 and IQualiV-Lung), ECOG-PS, anthropometric measurements, clinical and laboratory toxicity assessment and response evaluation. DISCUSSION: During palliative systemic therapy in advanced cancer patients, one of the main goals is the improvement and maintenance of HRQOL, which can be negatively affected by cancer symptoms, cancer- or treatment-related psychosocial difficulties, and chemotherapy toxicity. Thus, much research has been dedicated to the development of new and more effective and/or less toxic cancer therapies. The present study is justified by the testing of a novel food supplement that may reduce some toxicities, thus, having a potential positive impact on the HRQOL of lung cancer patients. The product in question (AferBio®) is already available for sale in Brazil, but has not yet been fully tested in cancer patients. TRIAL REGISTRATION: This Trial was registered on March 19, 2018 with ClinicalTrials.gov , NCT03469063. Protocol version: 2.0 from March 26, 2018. Trial status: Patient enrollment in the study began in April, 2018.


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brasil , Docetaxel/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Qualidade de Vida , Adulto Jovem
20.
In Vivo ; 33(3): 843-853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028207

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate the efficacy and safety of carboplatin/docetaxel combination therapy in patients with locally advanced and/or recurrent/metastatic (LA/RM) salivary gland carcinoma (SGC). MATERIALS AND METHODS: This was a retrospective analysis of 24 patients that included six patients with AR-positive salivary duct carcinoma (SDC) after progressive disease treated with combined androgen blockade (CAB). Carboplatin (AUC5) and docetaxel (70 mg/m2) were administered for six courses every three weeks. RESULTS: The overall response rate was 42%, the median progression-free survival was 8.4 months, and the median overall survival was 26.4 months. Among the six patients with CAB-resistant SDC, two achieved a partial response and two long-term stable disease. Grade 3/4 neutropenia and anemia were observed in 20-30% of the patients; all adverse events were manageable. CONCLUSION: Carboplatin/docetaxel combination therapy may be a chemotherapeutic option for patients with LA/RM SGC, and a valuable second-line chemotherapy for CAB-resistant, AR-positive SDC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carboplatina/administração & dosagem , Terapia Combinada , Docetaxel/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/mortalidade , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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