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1.
Gan To Kagaku Ryoho ; 47(10): 1471-1475, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33130743

RESUMO

This retrospective study aimed to evaluate the effect of the antiemetic drug olanzapine(OLZ)on blood sugar levels in patients treated with adjuvant or neoadjuvant chemotherapy(AC: doxorubicin plus cyclophosphamide or CEF: cyclophosphamide plus epirubicin plus fluorouracil) for breast cancer. Here, we evaluated the frequency of diabetes(postprandial blood sugar: PBS≥200 mg/dL)and the change in PBS in 149 patients who were prescribed OLZ between September 2016 and August 2017 at our hospital. No diabetic patients were identified during the observation period(median: 3 cycles of chemotherapy). Among the 95 patients with more than 2 PBS readings, no difference was observed in the incidence of increased PBS, regardless of the diabetic risk, before and after OLZ administration. This study therefore found that the short term use of OLZ as an antiemetic had little effect on PBS, suggesting that it can be used safely during treatment with AC or CEF.


Assuntos
Antieméticos , Neoplasias da Mama , Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Glicemia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Ciclofosfamida/efeitos adversos , Epirubicina/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Terapia Neoadjuvante , Olanzapina , Estudos Retrospectivos , Resultado do Tratamento
2.
Gan To Kagaku Ryoho ; 47(10): 1517-1520, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33130754

RESUMO

A 66-year-old male diagnosed with transverse colon cancer was admitted to our hospital. Computed tomography, colonoscopy, and esophagogastroduodenoscopy revealed locally advanced cancer with invasion of the gastric antrum. We staged the disease as cT4a, cN2, cM0, Stage ⅢB, with wild-type RAS expression. We performed an ileostomy prior to administering chemotherapy. The patient received 4 courses of modified FOLFOXIRI plus bevacizumab and 2 courses of FOLFIRI. The size of the tumor noticeably decreased after chemotherapy. The patient experienced grade 3 neutropenia, anorexia, and oral mucositis during chemotherapy. We performed a right hemicolectomy(D3), partial gastrectomy and ileum resection after administering neoadjuvant chemotherapy. The pathological stage of the disease was ypT2, ypN0, ypM0, ypStageⅠ, and the effect of the chemotherapy was Grade 1b. After the resection, he received mFOLFOX6 and CapeOX for 3 months as adjuvant chemotherapy. He remained cancer-free for 1 year and 3 months after the surgery. This result suggests that preoperative modified FOLFOXIRI plus bevacizumab chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.


Assuntos
Colo Transverso , Neoplasias do Colo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Fluoruracila/uso terapêutico , Humanos , Leucovorina , Masculino , Terapia Neoadjuvante , Compostos Organoplatínicos , Antro Pilórico
3.
Nat Commun ; 11(1): 5485, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127883

RESUMO

Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we present a machine-learning framework to identify robust drug biomarkers by taking advantage of network-based analyses using pharmacogenomic data derived from three-dimensional organoid culture models. The biomarkers identified by our approach accurately predict the drug responses of 114 colorectal cancer patients treated with 5-fluorouracil and 77 bladder cancer patients treated with cisplatin. We further confirm our biomarkers using external transcriptomic datasets of drug-sensitive and -resistant isogenic cancer cell lines. Finally, concordance analysis between the transcriptomic biomarkers and independent somatic mutation-based biomarkers further validate our method. This work presents a method to predict cancer patient drug responses using pharmacogenomic data derived from organoid models by combining the application of gene modules and network-based approaches.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Aprendizado de Máquina , Organoides/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Desenvolvimento de Medicamentos/métodos , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Organoides/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transcriptoma , Bexiga Urinária/efeitos dos fármacos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
4.
BMC Bioinformatics ; 21(Suppl 14): 364, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998700

RESUMO

BACKGROUND: Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients' primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. RESULTS: We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study's limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. CONCLUSIONS: Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.


Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Aprendizado de Máquina , Antineoplásicos/uso terapêutico , Área Sob a Curva , Análise por Conglomerados , Bases de Dados Genéticas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Curva ROC
5.
Am J Clin Oncol ; 43(9): 654-659, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889836

RESUMO

OBJECTIVE: By using the Korean Pancreatic Cancer (K-PaC) registry, we compared the clinical outcomes of FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) in patients with metastatic pancreatic cancer (MPC). METHODS: We constructed a web-based database of 3748 anonymized patients diagnosed with pancreatic ductal adenocarcinoma. MPC patients who received first-line FFX or GNP were enrolled. Overall survival (OS), progression-free survival, grade III to IV toxicity, and cross-over treatment were analyzed. RESULTS: A total of 413 patients (232 vs. 181, FFX vs. GNP; all data are presented in this sequence) were eligible. Median age was 63 years (60 vs. 69 y) with 43% (39% vs. 47%) comprising female individuals. The major metastatic sites were the liver (64%), peritoneum (25%), and distant lymph nodes (18%). The median OS was 11.5 versus 12.7 months (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.68-1.12, P=0.286), and median progression-free survival was 7.5 versus 8.1 months (HR=0.92, 95% CI: 0.70-1.20, P=0.517), respectively. The frequency of grade III to IV febrile neutropenia was higher in the FFX group (18% vs. 11%, P=0.040), and that of peripheral neuropathy was higher in the GNP group (8% vs. 14%, P=0.046). The chance to receive second-line chemotherapy was higher in the GNP group (45% vs. 56%, P=0.036). In the cross-over treatment, the median OS of the FFX-GNP group (n=43) and the GNP-FFX group (n=47) was 16.8 versus 17.7 months (HR=0.79, 95% CI: 0.44-1.41, P=0.425). CONCLUSIONS: FFX and GNP showed similar efficacy and comparable toxicity in MPC patients. Although the GNP group had a higher chance to receive second-line chemotherapy, they did not have improved overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Peritoneais/secundário , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/secundário , Estudos Cross-Over , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Neutropenia Febril/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Intervalo Livre de Progressão , Sistema de Registros , República da Coreia , Taxa de Sobrevida , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(36): e22060, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899071

RESUMO

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Antimetabólitos Antineoplásicos , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas/métodos , Irinotecano/uso terapêutico , Japão/epidemiologia , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Oxaliplatina/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/métodos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
7.
Anticancer Res ; 40(10): 5829-5835, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988912

RESUMO

BACKGROUND: Preoperative chemotherapy with surgery is the most effective treatment modality in Japan for advanced oesophageal squamous cell carcinoma (OSCC). We evaluated the long-term outcomes associated with preoperative docetaxel/cisplatin/5-fluorouracil (DCF) administration followed by oesophagectomy in OSCC. PATIENTS AND METHODS: Overall, 76 consecutive patients with cStage IB-IIIC OSCC were enrolled. After two cycles of preoperative DCF, oesophagectomy was performed. Survival monitoring was performed and relevant risk factors were analysed. RESULTS: The median follow-up period was 88.3 months. The 5-year overall and recurrence-free survival rates were 51% and 43%, respectively. In the multivariable analysis, cT3 stage [hazard ratio (HR)=1.81, 95% confidence interval (CI)=1.08-6.16], incomplete chemotherapy (HR=2.35, 95% CI=1.37-4.02), poor clinical response (HR=1.82, 95% CI=1.01-3.29), and postoperative complications (HR=2.11, 95% CI=1.14-3.90) were independent predictors of poorer overall survival. CONCLUSION: The 5-year outcomes of preoperative DCF with oesophagectomy were favourable. Our findings can aid in the formulation of strategies aimed at improving prognosis in OSCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Metástase Linfática/tratamento farmacológico , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Feminino , Fluoruracila/uso terapêutico , Humanos , Japão/epidemiologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
8.
Ann Surg ; 272(5): 779-785, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833766

RESUMO

OBJECTIVE: This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC. BACKGROUND: PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed. METHODS: This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis ("CROSS Eligibility") was performed based on tumor length, cT-stage, cM-stage, age, and performance status. RESULTS: One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For "CROSS Eligible subgroup," the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093). CONCLUSIONS: There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas/terapia , Esofagectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos
9.
BMC Surg ; 20(1): 174, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738882

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit selected HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 20 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely. CONCLUSIONS: IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Veia Porta , Trombose Venosa/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Cuidados Intraoperatórios , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Masculino , Compostos Organoplatínicos/uso terapêutico , Radioterapia Adjuvante , Estudos Retrospectivos , Trombectomia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/radioterapia , Trombose Venosa/cirurgia
10.
Am J Med Sci ; 360(3): 279-286, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32829780

RESUMO

BACKGROUND: The essential role of 6-phosphogluconate dehydrogenase (6PGD), the enzyme catalyzing the oxidative pentose phosphate pathway, in tumor growth and metabolism has garnered attention in recent years. In this work, we are the first to demonstrate that aberrant activation of 6PGD is a feature in renal cell carcinoma (RCC) and is critically involved in renal carcinogenesis and chemo- and immuno-resistance. MATERIALS AND METHODS: 6PGD expression and activity were systematically analyzed in normal and malignant renal cells and tissues. The roles of 6PGD and its downstream mechanism were investigated using gain-of-function and loss-of-function approaches. RESULTS: 6PGD expression and enzyme activity were increased in RCC cells and patients' samples. Activation of 6PGD via gain-of-function approach promoted growth of normal kidney but not RCC cells, and alleviated the efficacy of chemotherapeutic (e.g., 5-FU) and immunotherapeutic (e.g., IFN-α) agents. In contrast, 6PGD inhibition using siRNA knockdown and pharmacological inhibitor physcion augmented the inhibitory effects of 5-FU and IFN-α in RCC. Mechanistic studies demonstrated that 6PGD inhibition activated AMPK signaling, leading to ACC1 enzyme inhibition and reduction of lipid synthesis. In addition, 6PGD inhibition disrupted NADPH and NADH homeostasis in RCC cells as shown by the decreased level of NADPH and NADH, and suppressed SIRT-1 activity. AMPK inhibition by siRNA knockdown reversed the inhibitory effects of physcion, demonstrating that the effect of 6PGD inhibition is AMPK activation dependent. CONCLUSIONS: Our work provides preclinical evidence that 6PGD inhibition may represent a potential therapeutic strategy to augment the efficacy of RCC standard of care drugs.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma de Células Renais/terapia , Reprogramação Celular/fisiologia , Neoplasias Renais/terapia , Fosfogluconato Desidrogenase/metabolismo , Transdução de Sinais/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Linhagem Celular , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Fluoruracila/uso terapêutico , Técnicas de Silenciamento de Genes , Humanos , Imunoterapia , Interferon-alfa/uso terapêutico , Rim/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , NADP/fisiologia , Fosfogluconato Desidrogenase/antagonistas & inibidores , Fosfogluconato Desidrogenase/genética , RNA Interferente Pequeno , Regulação para Cima
11.
PLoS One ; 15(8): e0237453, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32780766

RESUMO

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is the most common ocular surface tumour. Diagnosis and management have traditionally been by excision biopsy. Recently there has been success with the use of topical chemo or immunotherapy, which has resulted in a move from invasive diagnosis by histology to an array of non-invasive diagnostic tests. METHODS: This observational study aims to describe the characteristics of patients with OSSN at St John Eye Hospital in Johannesburg, South Africa. Non-invasive diagnostic tests (impression cytology, anterior segment-OCT, methylene blue staining) will be compared to the gold standard, histology. Treatment success, recurrence and adverse events will be documented between three treatment options that include: surgical excision, topical 5-Fluorouracil (5FU) chemotherapy, and topical 5FU with retinoic acid therapy. DISCUSSION: There is a trend to the use of less invasive diagnosis and management for OSSN. Minimally invasive diagnostic tests include cytology, anterior-segment OCT and methylene blue staining. The study will compare these to the gold standard histology, thereby providing evidence for their use in clinical practice. Interferon alpha 2b is commonly used as immunotherapy for OSSN. The cost of this medication is prohibitive to its adoption in a developing country. We therefore decided to use 5FU as the chemotherapeutic agent of choice in this study. The success, adverse events and recurrence rates with this agent may provide additional evidence for its use in the management of OSSN. Overall, if diagnosis and management can be implemented with good success in the outpatient environment, care can be improved for this condition in a developing country.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Oculares/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Área Sob a Curva , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/etiologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Curva ROC , Fatores de Risco , África do Sul , Centros de Atenção Terciária , Tomografia de Coerência Óptica , Resultado do Tratamento , Raios Ultravioleta/efeitos adversos
12.
Surgery ; 168(3): 440-447, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641278

RESUMO

BACKGROUND: More than 70% of patients with localized pancreatic cancer treated with upfront surgery develop disease recurrence. Herein we describe the radiographic patterns and timing of disease recurrence after neoadjuvant therapy and surgery in patients with pancreatic cancer. METHODS: Radiographic patterns of first disease recurrence were examined in patients with localized pancreatic cancer who completed neoadjuvant therapy and surgery. Disease recurrence was classified as local (pancreas, resection bed, or peripancreatic vasculature); regional (peritoneum or abdominal wall); or distant (liver, lung, bone). Progression-free survival was calculated from the date of diagnosis to the date of recurrence. RESULTS: Of 306 consecutive patients who completed neoadjuvant therapy and surgery, 149 (49%) had resectable pancreatic cancer and 157 (51%) had borderline resectable disease. Neoadjuvant therapy consisted of chemoradiation (32%), chemotherapy (14%), or both therapies (54%). Overall, primary therapy (including preoperative and postoperative therapy) consisted of chemoradiation alone in 29 (9%), chemotherapy alone in 14 (5%), and both therapies in 263 (86%) patients. At a median follow-up of 27 months, 186 (61%) of the 306 patients had recurrent pancreatic cancer. Sites of first recurrence were local-only in 29 (9%), regional-only in 19 (6%), distant-only in 87 (28%), and multisite in 51 (17%). The overall median progression-free survival for all patients was 24 months. Neoadjuvant chemoradiation reduced the odds of local-only recurrence (odds ratio: 0.21; 95% confidence interval: 0.06-0.77; P = .02). CONCLUSION: After neoadjuvant therapy and surgery, 9% of patients were found to have local-only recurrence. Treatment sequencing that incorporates neoadjuvant chemoradiation may improve local disease control.


Assuntos
Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Pâncreas/diagnóstico por imagem , Pancreatectomia , Neoplasias Pancreáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Quimiorradioterapia/estatística & dados numéricos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Irinotecano/uso terapêutico , Estimativa de Kaplan-Meier , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Oxaliplatina/uso terapêutico , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Intervalo Livre de Progressão , Radiografia/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
13.
Anticancer Res ; 40(8): 4763-4771, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727803

RESUMO

BACKGROUND/AIM: Chemoimmunotherapy is a promising treatment for various malignant diseases. In this study, we examined whether first-line chemoimmunotherapy using adoptive immune-cell therapy was effective for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: The therapeutic efficacy and safety of the standard first-line chemoimmunotherapy with adoptive αß T cell therapy and bevacizumab were assessed using thirty-two patients with mCRC in our hospital. Immunological status after this chemoimmunotherapy was also evaluated. RESULTS: The response and disease control rates were 68.8% and 87.5%, respectively. Further, median progression-free and overall survival were 14.2 and 35.3 months. Immunotherapy-associated toxicity was minimal. Significant decrease in the change of monocyte number (p=0.006) and increase in the change of rate of lymphocyte-to-monocyte ratio (p=0.039) were seen in the complete response group. CONCLUSION: First-line chemoimmunotherapy with adoptive αß T cell therapy may be useful for mCRC.


Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Imunoterapia/métodos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Intervalo Livre de Progressão
14.
Anticancer Res ; 40(8): 4773-4777, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727804

RESUMO

BACKGROUND/AIM: Recent studies have demonstrated the efficacy of salvage surgery following downstaging of hepatocellular carcinoma (HCC). The aim was to assess the outcomes of salvage surgery after successful downstaging using hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: Patients whose diagnosis was unresectable locally advanced HCC and who were resected after conversion to a resectable status by HAIC were included. The overall survival (OS) rate, and disease-free survival (DFS) rate were analyzed by stratifying patients into those with Vp3/4, Vv2/3, and those without major vascular invasion (MVI). RESULTS: Eighteen patients were censored. Among them, six patients had Vp3/4, four patients had Vv2/3, and eight patients had no MVI. The 5-year OS rates of patients with Vp3/4 and those without MVI were 83% and 73%, respectively, whereas those with Vv2/3 had 0% (p<0.001). CONCLUSION: Salvage surgery has the potential to provide excellent outcomes in resectable HCC patients, except for those with Vv2/3.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Hepatectomia/métodos , Humanos , Infusões Intra-Arteriais/métodos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Taxa de Sobrevida , Resultado do Tratamento
15.
Anticancer Res ; 40(7): 3659-3667, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620605

RESUMO

BACKGROUND/AIM: FOLFIRINOX [fluorouracil (5-FU), irinotecan, oxaliplatin] and gemcitabine plus nab-paclitaxel are standard treatments for patients with pancreatic ductal adenocarcinoma (PDAC). Despite efficacy rates of less than 32%, evidence is lacking to guide the use of one drug over the other. Herein, we compared the sensitivity of patient-derived PDAC cell lines to each of these regimens. MATERIALS AND METHODS: Changes in the growth of 19 low-passage patient-derived PDAC cell lines were evaluated in response to treatment with FOLFIRINOX and gemcitabine plus paclitaxel (Gem-Pac). RESULTS: Six cell lines exhibited optimal sensitivity (high EMax and low GI50) to FOLFIRINOX and three cell lines exhibited optimal sensitivity to Gem-Pac. Several cell lines that were optimally sensitive to one drug regimen exhibited very poor response to the other. CONCLUSION: Further characterization of cancer cells exhibiting preferential sensitivity to each of these regimens may allow the identification of biomarkers to guide the selection of appropriate chemotherapy for a given patient.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico
16.
Anticancer Res ; 40(7): 4011-4015, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620645

RESUMO

BACKGROUND/AIM: The aim of this monocentric study was to evaluate the efficacy and tolerability of a polychemotherapy regimen based on gemcitabine, docetaxel, capecitabine, cisplatin (PDGX) as second-line for advanced pancreatic cancer after FOLFIRINOX. PATIENTS AND METHODS: Patients received FOLFIRINOX as first-line regimen were retrospectively identified between January 2016 and January 2019. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were treated in our center by PDGX. RESULTS: During this period, 18 patients received PDGX regimen as second-line therapy. Main grade 3 toxicities were hematologic, which required dose adaptation in 14/18 patients. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2,91 and 5,3 months, respectively. Total OS from the initiation of first-line was and 11,9 months. CONCLUSION: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Docetaxel/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Resultado do Tratamento
17.
Anticancer Res ; 40(7): 4029-4032, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620648

RESUMO

The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. This is a case report of a 70-year-old female with a history of skin squamous cell carcinoma presenting with occult hematochezia. Colonoscopy and biopsy results confirmed a microsatellite stable (MMS) adenocarcinoma in the ascending colon, and subsequent computed tomography (CT) scans identified a 3.2 cm right colonic mass and a 5.0 cm mass in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the presence of pancreatic ductal adenocarcinoma (PDAC). The patient underwent neo-adjuvant FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) chemotherapy prior to the simultaneous distal pancreatectomy and right hemicolectomy for both pancreatic and colonic tumors. The pathology diagnoses included moderately differentiated pancreatic ductal carcinoma (PDAC) with histiocyte-like features (tumor stage: ypT3N1M0) and moderately differentiated colonic adenocarcinoma, intestinal type (tumor stage: ypT3N0M0). To the best of our knowledge, this is the first documented case of synchronous primary colonic adenocarcinoma and PDAC in the English literature.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Escamosas , Neoplasias do Colo/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Primárias Múltiplas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Cutâneas
18.
Clin Nucl Med ; 45(9): 707-708, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657876

RESUMO

Triplet chemotherapy (FOLFOXIRI) + bevacizumab regimen is indicated as first-line treatment of BRAF-mutated metastatic colorectal cancer (mCRC). Nevertheless, its proven therapeutic efficacy in clinical trials was solely based on partial morphologic responses assessed by CT. To date, only 1 case of complete response assessed by FDG PET/CT was reported in literature in BRAF-mutated mCRC, but treated with doublet chemotherapy (FOLFIRI) + cetuximab regimen. We report a complete metabolic response assessed by FDG PET/CT, maintained over time (13 months) in a 60-year-old woman with BRAF-mutated mCRC treated by FOLFOXIRI-bevacizumab. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Fluordesoxiglucose F18 , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas B-raf/genética , Camptotecina/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento
20.
Int J Nanomedicine ; 15: 3333-3346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494133

RESUMO

Background and Objective: Cancer cells accumulate high concentrations of reactive oxygen species as a result of their faster and uninhibited metabolic activity. Cancer chemotherapeutic agents release an excess of severe adverse reactions as a result of targeting normal cells. This demands an improvement in targeted drug-delivery systems to selectively discharge anticancer drugs in the vicinity of such highly metabolically and mitotically active cells. Materials and Methods: Here, magnetic nanoparticles were synthesized by a traditional co-precipitation technique. Fe3O4@OA-CS-5-FLU-NPs were synthesized by an easy and rapid in situ loading method. The proposed Fe3O4@OA-CS-5-FLU-NPs were productively prepared as well as characterized by various spectroscopic and microscopic studies. Results: The targeted drug release profile of the Fe3O4@OA-CS-5-FLU-NPs was studied in the presence of ROS including H2O2 and pH induction. The released product, Fe3O4@OA-CS-5-FLU-NP, exhibited desirable levels of cytotoxicity and demonstrated morphological changes and inhibition of colony formation for A549 and HeLa S3 cancer cells. The IC50 values at 24 hours were 12.9 and 23 µg/mL, respectively. Conclusion: In summary, results from the MTT assay, fluorescence staining as well as colony formation assays, revealed that the Fe3O4@OA-CS-5-FLU-NPs were active and safe for anticancer biomedical applications. In summary, the present investigation provides a powerful nanostructured based system for improved cancer theranostics that should be further studied.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Nanopartículas de Magnetita/ultraestrutura , Neoplasias/patologia , Ácido Oleico/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
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