Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 309
Filtrar
1.
Arq. ciências saúde UNIPAR ; 27(1): 493-510, Jan-Abr. 2023.
Artigo em Português | LILACS | ID: biblio-1416551

RESUMO

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.


Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.


La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pacientes , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cuidados Paliativos , Preparações Farmacêuticas , Carboplatina/efeitos adversos , Paclitaxel/efeitos adversos , Diabetes Mellitus , Interações Medicamentosas , Hipertensão , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico
2.
Chinese Journal of Oncology ; (12): 178-184, 2022.
Artigo em Chinês | WPRIM | ID: wpr-935199

RESUMO

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.


Assuntos
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Paclitaxel/uso terapêutico , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia
3.
Journal of Peking University(Health Sciences) ; (6): 686-691, 2021.
Artigo em Chinês | WPRIM | ID: wpr-942237

RESUMO

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.


Assuntos
Idoso , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Docetaxel/uso terapêutico , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resultado do Tratamento
5.
Journal of Gynecologic Oncology ; : 15-2020.
Artigo em Inglês | WPRIM | ID: wpr-811217

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533


Assuntos
Humanos , Alopecia , Carboplatina , Estudos de Coortes , Intervalo Livre de Doença , Doxorrubicina , Tratamento Farmacológico , Seguimentos , Síndrome Mão-Pé , Coreia (Geográfico) , Neoplasias Ovarianas , Paclitaxel , Doenças do Sistema Nervoso Periférico , Platina , Prognóstico , Recidiva , Estudos Retrospectivos
6.
Journal of Gynecologic Oncology ; : 23-2020.
Artigo em Inglês | WPRIM | ID: wpr-811212

RESUMO

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.


Assuntos
Humanos , Carboplatina , Intervalo Livre de Doença , Tratamento Farmacológico , Terapia Neoadjuvante , Neutropenia , Neoplasias Ovarianas , Paclitaxel , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
7.
Rev. Hosp. Ital. B. Aires (2004) ; 39(4): 146-148, dic. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1099838

RESUMO

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)


Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Imunoterapia/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Tiroxina/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Tireotropina/análise , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Supressoras de Tumor/efeitos dos fármacos , Dermatologia , Traumatismos Faciais , Paralisia Facial , Antígeno CTLA-4/efeitos dos fármacos , Antígeno CTLA-4/fisiologia , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/fisiologia , Pemetrexede/administração & dosagem , Melanoma/complicações , Melanoma/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Metástase Neoplásica/tratamento farmacológico
8.
Chinese Journal of Contemporary Pediatrics ; (12): 1193-1197, 2019.
Artigo em Chinês | WPRIM | ID: wpr-781713

RESUMO

OBJECTIVE@#To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG).@*METHODS@#A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy.@*RESULTS@#The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P0.05). No chemotherapy-related death was observed in either group.@*CONCLUSIONS@#Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.


Assuntos
Criança , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carboplatina , Glioma do Nervo Óptico , Estudos Retrospectivos , Vincristina
9.
Journal of Gynecologic Oncology ; : e82-2019.
Artigo em Inglês | WPRIM | ID: wpr-764516

RESUMO

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18–70 years who had International Federation of Gynecology and Obstetrics stage IIB–IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82–1.96; p=0.293) and 1.42 (95% CI=0.81–2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164 Thai Clinical Trials Registry Identifier: TCTR 20140106001


Assuntos
Humanos , Braço , Povo Asiático , Carboplatina , Quimiorradioterapia , Quimioterapia Adjuvante , Cisplatino , Intervalo Livre de Doença , Seguimentos , Ginecologia , Linfonodos , Obstetrícia , Paclitaxel , Recidiva , Estatística como Assunto , Neoplasias do Colo do Útero
10.
Cancer Research and Treatment ; : 1117-1127, 2019.
Artigo em Inglês | WPRIM | ID: wpr-763168

RESUMO

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.


Assuntos
Animais , Feminino , Humanos , Camundongos , Carboplatina , Causas de Morte , Tratamento Farmacológico , Exoma , Expressão Gênica , Genoma , Xenoenxertos , Razão de Chances , Neoplasias Ovarianas , Ovário , Paclitaxel , Recidiva , Análise de Sequência de RNA , Estatística como Assunto
11.
Obstetrics & Gynecology Science ; : 285-289, 2019.
Artigo em Inglês | WPRIM | ID: wpr-760645

RESUMO

The long-term survival of heavily pretreated patients with primary peritoneal cancer (PPC) is uncommon. Here, we report on a patient with PPC refractory to multiple lines of intravenous chemotherapy, namely, a combined regimen of paclitaxel and carboplatin, and single regimens of topotecan, docetaxel, cisplatin, and gemcitabine. However, after intraperitoneal (IP) chemotherapy with paclitaxel-cisplatin, the patient's condition improved, and she has been progression-free for more than 4 years. Interestingly, before the IP chemotherapy, the recurrences were limited to the peritoneal cavity. These results suggest that IP recurrence might be a predictor of a good response to IP chemotherapy.


Assuntos
Humanos , Carboplatina , Cisplatino , Tratamento Farmacológico , Infusões Parenterais , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Paclitaxel , Cavidade Peritoneal , Neoplasias Peritoneais , Recidiva , Topotecan
12.
China Journal of Chinese Materia Medica ; (24): 5231-5239, 2019.
Artigo em Chinês | WPRIM | ID: wpr-1008388

RESUMO

The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.


Assuntos
Humanos , Artesunato/uso terapêutico , Carboplatina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Neoplasias/radioterapia , Radiossensibilizantes/uso terapêutico
13.
Biol. Res ; 52: 13, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1011415

RESUMO

BACKGROUND: Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. METHODS: The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. RESULTS: Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. CONCLUSION: CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/3-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.


Assuntos
Humanos , Feminino , Neoplasias Ovarianas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Carboplatina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Transcriptoma/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Fenótipo , Transdução de Sinais , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Análise de Sequência de RNA , Linhagem Celular Tumoral , Transcriptoma/genética
14.
Autops. Case Rep ; 8(2): e2018025, Apr.-May 2018. ilus
Artigo em Inglês | LILACS | ID: biblio-905609

RESUMO

Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal tract, although they are potentially ubiquitous throughout the body. Primary unknown NET has a worse prognosis and shorter survival comparing with other NETs, with limited available data in the literature concerning this subgroup. The authors report the case of large-cell NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two infracentimetric lung lesions that could not be accessed for biopsy and were negative at both somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed with three mediastinal masses, so the patient was started on chemotherapy with carboplatin and etoposide with initial total response. Early progression showed no response to further chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated with local radiotherapy. This patient has an atypical long survival (54 months) compared to the literature data. In fact, there are few long-term survivors of large-cell NET and they are all related to complete surgical resection.


Assuntos
Humanos , Feminino , Idoso , Carcinoma Neuroendócrino , Neoplasias Primárias Desconhecidas , Carboplatina/uso terapêutico , Carcinoma de Células Grandes , Etoposídeo/uso terapêutico , Tumores Neuroendócrinos
15.
Rev. peru. med. exp. salud publica ; 35(1): 46-54, ene.-mar. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-961861

RESUMO

RESUMEN Objetivos. Determinar la tasa de citorreducción óptima en pacientes con cáncer de ovario avanzado que recibieron quimioterapia neoadyuvante con carboplatino y paclitaxel dosis densa seguido de cirugía de citorreducción de intervalo (CCI). Materiales y métodos. Estudio de una serie de casos retrospectiva de mujeres peruanas tratadas con quimioterapia neoadyuvante con carboplatino (AUC 6 mg/ml/min) y paclitaxel (80 mg/m2 semanal) seguido de CCI, en el Instituto Nacional de Enfermedades Neoplásicas durante el período 2010-2014. Resultados . Los 41 pacientes que alcanzaron cirugía de intervalo, tuvieron una mediana de edad de 59 años (rango: 47-73 años). En 37 (90,2%) pacientes se reportó histología de adenocarcinoma seroso de alto grado. Treinta y cuatro (82,9%) lograron citorreducción óptima y cinco (14,7%) respuesta patológica completa. La sobrevida libre de progresión al año y 2 años fueron 74,7% y 51,8%, respectivamente. La sobrevida global al año y 2 años fue 85,2% y 71,4%, respectivamente. El riesgo de progresión y muerte fue mayor en pacientes sin citorreducción óptima y pacientes con niveles de dosaje del antígeno carcinoembrionario 125 postoperatorio > 30 U/ml. Conclusiones . La neoadyuvancia con carboplatino y paclitaxel dosis densa logró una frecuencia elevada de citorreducción óptima. Los niveles de antígeno carcinoembrionario 125 postoperatorios y citorreducción óptima resultaron factores independientes de sobrevida libre de progresión y sobrevida global.


ABSTRACT Objectives. To determine the rate of optimal cytoreduction in patients with advanced ovarian cancer who received neoadjuvant chemotherapy with dose-dense carboplatin and paclitaxel followed by interval debulking surgery (IDS). Materials and Methods. A retrospective study of a series of cases of Peruvian women treated with neoadjuvant chemotherapy with carboplatin (6 AUC mg/mL/min) and paclitaxel (80 mg/m2 weekly) followed by IDS, at the National Institute of Neoplastic Diseases during the 2010-2014 period. Results. The 41 patients who made it to the interval surgery had a median age of 59 years (range: 47-73 years). In 37 (90.2%) patients, high-grade serous adenocarcinoma histology was reported. Thirty-four (82.9%) achieved optimal cytoreduction and five (14.7%), a complete pathological response. Progression-free survival at one year and two years was 74.7% and 51.8%, respectively. Overall survival at one year and two years was 85.2% and 71.4%, respectively. The risk of progression and death was greater in patients without optimal cytoreduction and in patients with postsurgery levels of carcinoembryonic antigen 125 > 30 U/mL. Conclusions. Neoadjuvant therapy with dose-dense carboplatin and paclitaxel achieved an elevated frequency of optimal cytoreduction. The post-surgery levels of carcinoembryonic antigen 125 and optimal cytoreduction were independent factors of progression-free survival and overall survival.


Assuntos
Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Carboplatina/administração & dosagem , Paclitaxel/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Antineoplásicos/administração & dosagem , Neoplasias Ovarianas/patologia , Peru , Institutos de Câncer , Estudos Retrospectivos , Resultado do Tratamento , Terapia Combinada , Terapia Neoadjuvante , Estadiamento de Neoplasias
16.
Journal of Gynecologic Oncology ; : e96-2018.
Artigo em Inglês | WPRIM | ID: wpr-718161

RESUMO

The 3-weekly regimen of carboplatin and paclitaxel is the backbone of first line adjuvant chemotherapy for advanced ovarian cancer. The landmark Japanese Gynaecologic Oncology Group (JGOG) 3016 study demonstrated significant improvements in progression-free survival and overall survival with dose dense weekly administration of paclitaxel in combination with 3-weekly carboplatin. However, efforts to replicate these benefits have failed in subsequent phase III trials. Weekly paclitaxel is purported to have enhanced antitumor activity, with stronger anti-angiogenic effects, and yet is better tolerated. In this review, we explore the rationale for dose dense weekly paclitaxel, and compare the relevant trials as well as quality of life considerations. Possible reasons for the difference in outcomes between the JGOG 3016 and other studies are reviewed, with a focus on how the addition of bevacizumab, the variations between histological and molecular subtypes of epithelial ovarian cancers, and ethnic pharmacogenetic differences may potentially affect the efficacy of dose dense paclitaxel.


Assuntos
Humanos , Bevacizumab , Carboplatina , Quimioterapia Adjuvante , Intervalo Livre de Doença , Tratamento Farmacológico , Neoplasias Ovarianas , Paclitaxel , Farmacogenética , Qualidade de Vida
17.
Journal of Gynecologic Oncology ; : e77-2018.
Artigo em Inglês | WPRIM | ID: wpr-716714

RESUMO

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2–3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with “no rescue antiemetic medication” and “no clinically significant nausea” or “only mild nausea” in the delayed phase (24–120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: “no vomiting” and “no rescue antiemetic medication”) in the acute (0–24 hours), delayed (24–120 hours), and overall (0–120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).


Assuntos
Feminino , Humanos , Antieméticos , Carboplatina , Dexametasona , Tratamento Farmacológico , Neoplasias dos Genitais Femininos , Incidência , Japão , Náusea , Vômito
18.
Cancer Research and Treatment ; : 691-700, 2018.
Artigo em Inglês | WPRIM | ID: wpr-715836

RESUMO

PURPOSE: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. MATERIALS AND METHODS: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively. RESULTS: In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity. CONCLUSION: These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.


Assuntos
Humanos , Ásia , Povo Asiático , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Grupos Raciais , Diarreia , Intervalo Livre de Doença , Tratamento Farmacológico , Incidência , Linfoma , Náusea , Pemetrexede , Fosfotransferases , Transtornos da Visão
19.
The Korean Journal of Internal Medicine ; : 541-551, 2018.
Artigo em Inglês | WPRIM | ID: wpr-714638

RESUMO

BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.


Assuntos
Animais , Feminino , Humanos , Camundongos , Apoptose , Carboplatina , Caspase 3 , Catalase , DNA , Tratamento Farmacológico , Glutationa , Hiperóxia , Neoplasias Pulmonares , Pulmão , Estresse Oxidativo , RNA Mensageiro , Superóxido Dismutase , Carga Tumoral
20.
Chinese Journal of Gastrointestinal Surgery ; (12): 1019-1024, 2018.
Artigo em Chinês | WPRIM | ID: wpr-691284

RESUMO

<p><b>OBJECTIVE</b>To evaluate the short-term efficacy and safety of neoadjuvant synchronous chemoradiotherapy (paclitaxel plus carboplatin regimen) in stage III adenocarcinoma of esophagogastric junction (AEG).</p><p><b>METHODS</b>Forty cases clinically diagnosed as stage III AEG were prospectively enrolled at the Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Hebei North University from December 2014 to November 2017 and then were randomly divided into paclitaxel plus carboplatin combined with synchronous radiotherapy group(neoadjuvant group) and direct operation group. Inclusion criteria was as follows:(1) AEG was diagnosed by gastroscopic biopsy and III stage was confirmed by ultrasound endoscopy and spiral CT;(2) physical strength score ≥70, and age ≤75 years old; (3) no contraindications of chemoradiotherapy and operation. Exclusion criteria was as follows:(1) patients voluntarily withdrew or refused the treatment;(2) occurrence of severe anaphylaxis; (3) uncontrollable events happened during treatment and treatment was unable to continue;(4) tumor developed obviously during treatment. Preoperative neoadjuvant synchronous chemoradiotherapy used TP regimen: paclitaxel 80 mg/m², drug concentration-time area under curve of carboplatin= 1.5 mg×ml⁻¹×min⁻¹, once per week for 9 weeks; radiotherapy began at the second week, 40 Gy/20 F, completed within 4 weeks. Operative procedure of both groups was radical resection of cardiac cancer(D2). Postoperative chemotherapy regimen was oral Tegafur(Gimeracil and Oteracil potassium). The side effects, diet situation, change of gastroscopic image after treatment in patients of neoadjuvant group were observed and efficacy evaluation of chemotherapy was performed according to solid tumor efficacy evaluation criteria of US National Cancer Institute. Operation-associated parameters, including R0 resection rate, lymph node metastasis, operative mortality and postoperative complications, were compared between two groups.</p><p><b>RESULTS</b>There were no significant differences in baseline information between the two group (all P>0.05). One case in neoadjuvant group was excluded because of perforation at lesion site 7 weeks after chemotherapy. The side effects of 19 cases in neoadjuvant group were mainly alopecia (100%) and marrow inhibition (68.4%), while 3-4 degree side effects were alopecia(8/19,42.1%), leukopenia (3/19, 15.8%) and neutropenia(3/19, 15.8%). Complete remission was observed in 4 cases; partial remission was observed in 13 cases and stable disease in 2 cases, with an objective response rate of 89.5% and a disease control rate of 100%. Before neoadjuvant chemotherapy, 16 cases were difficult to take liquid diet and 3 cases received liquid diet only, while after 12 weeks of neoadjuvant chemotherapy, all the 19 cases received normal diet. Besides, after neoadjuvant chemotherapy, gastroscopic examination showed close healing of cardiac ulcer, disappearance of swelling, and renewal of normal mucosa. Compared to direct operation group, neoadjuvant group had less number of positive lymph node (4.9±3.6 vs. 8.8±2.8, P<0.05) and higher R0 resection rate (94.7% vs. 50.0%, P<0.05). Total number of harvested lymph node was not significantly different between two groups (19.1±2.5 vs. 18.6±7.0, t=0.326, P=0.746). There was no surgical death in either group. One case in direct operation group developed postoperative inflammatory obstruction. No associated complication was found in neoadjuvant group.</p><p><b>CONCLUSION</b>Paclitaxel plus carboplatin combined with synchronous radiotherapy can elevate the R0 resection rate of patients with stage III esophagogastric junction adenocarcinoma, without increasing operative mortality and postoperative complications.</p>


Assuntos
Idoso , Humanos , Adenocarcinoma , Tratamento Farmacológico , Terapêutica , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Carboplatina , Quimiorradioterapia , Neoplasias Esofágicas , Terapêutica , Junção Esofagogástrica , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel , Neoplasias Gástricas , Terapêutica , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA