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Combining chemotherapy with immunotherapy improves the therapeutic outcome for first-line (1L) patients with advance nonsmall-cell lung cancer (NSCLC). Two cohorts of a phase 1b study (NCT02937116) aimed to evaluate the safety and efficacy of sintilimab, a PD-1 inhibitor, plus chemotherapy in 1L patients with nonsquamous and squamous NSCLC (nsqNSCLC/sqNSCLC); and to identify potential biomarkers for treatment response. Treatment-naïve patients with nsqNSCLC were enrolled and intravenously given sintilimab (200 mg), pemetrexed (500 mg/m2), and cisplatin (75 mg/m2), every 3 weeks (Q3W) for 4 cycles in cohort D. Treatment-naïve patients with sqNSCLC were enrolled and intravenously given sintilimab (200 mg), gemcitabine (1250 mg/m2), and cisplatin (75 mg/m2), Q3W, for 6 cycles in cohort E. The primary objective was to evaluate the safety and efficacy of the treatment. The additional objective was to explore biomarkers for the treatment efficacy. Twenty-one patients with nsqNSCLC, and 20 patients with sqNSCLC were enrolled in cohort D and cohort E, respectively. By the data cutoff (April 17, 2019), 8 (38.1%) patients in cohort D and 17 (85.0%) patients in cohort E experienced grade 3-4 adverse events. The median follow-up duration was 16.4 months (14.8-23.0) in cohort D and 15.9 months (11.7-17.7) in cohort E. The objective response rate was 68.4% (95% CI 43.4%, 87.4%) in cohort D and 64.7% (95% CI 38.3%, 85.8%) in cohort E. Neither PD-L1 expression nor tumor mutation burden value was significantly associated with an improved treatment response. Sintilimab plus chemotherapy exhibited manageable toxicity and an encouraging antitumor activity in patients with nsqNSCLC and sqNSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
BACKGROUND: Sintilimab blocks the interaction between programmed death-1 (PD-1) and its ligands. The safety and efficacy of sintilimab combined with oxaliplatin/capecitabine (CapeOx) as first-line treatment were evaluated in patients with gastric (G)/gastroesophageal junction (GEJ) adenocarcinoma in a phase Ib clinical trial. METHODS: Patients with locally advanced or metastatic G/GEJ adenocarcinoma without previous systemic treatment were enrolled as one cohort of a multi-cohort study. Sintilimab was administered at a dose of 200 mg intravenously (IV) in combination with CapeOx (1000 mg/m2 capecitabine orally, bid, D1-14 and 130 mg/m2 oxaliplatin IV, D1) every 21 days for up to 6 cycles. After combination treatment, patients continued to receive sintilimab (200 mg) at 3 weekly intervals as maintenance therapy until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent, or for up to 24 months. Adverse events (AEs) were monitored to assess safety in terms of their frequency, intensity and causality. The efficacy endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Tumor mutation burden (TMB) was evaluated for its association with clinical response. RESULTS: A total of 20 patients were enrolled and received sintilimab plus CapeOx. All patients reported treatment-related AEs (TRAEs). Grade 3-4 TRAEs were found in 11 (55.0%) patients. Seventeen patients obtained partial response and the ORR was 85.0% (95% CI: 62.1-96.8%). Three (15.0%) had stable disease and DCR was 100.0% (95% CI: 83.2-100.0%). As data cutoff of May 1, 2019, the median follow-up was 7.8 months. The median PFS was 7.5 months (95% CI: 6.2-9.4) and median OS had not been reached. The OS rates at 6 months and 12 months were 100.0 and 68.0%. No association was observed between TMB and efficacy. CONCLUSIONS: Sintilimab combined with CapeOx as first-line treatment demonstrated acceptable safety and promising efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02937116 . Registered 8 October 2016.
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Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Junção Esofagogástrica/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Índice de Gravidade de Doença , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
A novel method to measure three-dimensional deformation based on defocused images of an object is presented in this paper. To do this, images of an object with artificial speckle features are taken by a camera. The in-plane coordinates of the points on a specimen surface are obtained according to the camera setup parameters and the defocused distance. The blur band width on the edges of the surface textures is used as a parameter to evaluate the blur degree of an image. Depth dimension is obtained by the relationship of the defocused distance and the blur degree. The relationship is given theoretically and experimentally. The digital image correlation method is used to trace each point on the specimen surface before and after deformation. Three-dimensional deformation can be obtained according to the displacement of each point. Reliability of the method is validated by two experiments.
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What we believe is a novel method to measure the dimension of an object with one defocused photo of an object is presented in this paper. To do this, a photo of the object is taken by a camera. The focal plane is chosen as a reference plane. The coordinates of the object surface are obtained by using the camera's parameters and corresponding defocused distance. The depth from the reference plane is obtained by evaluating the confusion degree of the photo around an edge. The relationship between the confusion degree and the distance from the reference plane has been given theoretically and experimentally. Several objects have been measured with the method, and it is shown that the results obtained are reliable. For nontextured surfaces, the edges of objects can be used to make the measurement.
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BACKGROUND: Clostridium difficile carriage has been considered as a potential source for the deadly infection, but its role in cancer patients is still unclear. We aimed to identify the clinical and immunological factors that are related to C. difficile carriage in Chinese cancer patients. METHODS: A total of 400 stool samples were collected from cancer patients who received chemotherapy in three hospitals of eastern China. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. PCR ribotyping was performed using capillary gel electrophoresis. Concentrations of prostaglandin E2 (PGE2), transforming growth factor beta (TGF-ß) and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Eighty-two (20.5%) samples were confirmed to be C. difficile-positive and positive for tpi, tcdA, and tcdB genes. The C. difficile-positive rates in patients with diarrhea and no diarrhea were 35% and 19.7%, respectively (p = 0.09). Patients who were younger than 50 years old and were hospitalized for at least 10 days had a C. difficile-positive rate as high as 35%. In contrast, patients who were older than 50 years old and were hospitalized for less than 10 days had a C. difficile-positive rate of only 12.7% (p = 0.0009). No association was found between C. difficile carriage and chemotherapy regimen, antibiotic drug use, or immunosuppressive mediators, such as prostaglandin E2 (PGE2), transforming growth factor beta (TGF-ß), or interleukin-10 (IL-10). Twelve ribotypes of C. difficile were identified, but none of them belonged to ribotype 027. CONCLUSIONS: We conclude that younger patients and those with longer hospitalization stays may be more prone to C. difficile carriage. Studies of larger populations are warranted to clarify the exact role of C. difficile carriage in hospitalized cancer patients in China.
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Portador Sadio/epidemiologia , Clostridioides difficile/genética , Diarreia/epidemiologia , Enterocolite Pseudomembranosa/epidemiologia , Neoplasias/epidemiologia , Toxinas Bacterianas/genética , Portador Sadio/diagnóstico , Portador Sadio/microbiologia , China , DNA Bacteriano/genética , Diarreia/diagnóstico , Diarreia/microbiologia , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/microbiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitalização , Humanos , Interleucina-10/genética , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Neoplasias/microbiologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , RibotipagemRESUMO
Accurate diagnosis and effective antiviral treatments are urgently needed for the prevention and control of flu caused by influenza viruses. In this study, a novel oleanic acid (OA) functionalized gold nanorod OA-AuNP was prepared through a convenient ligand-exchange reaction. As hemagglutinin (HA) on the viral surface binds strongly to the multiple OA molecules on the surface of the nanoparticle, the prepared OA-AuNP was found to exhibit potent antiviral activity against a wide range of influenza A virus strains. Furthermore, the change in color resulting from the specific binding between HA and OA and the resultant aggregation of the OA-AuNP can be visually observed or measured by UV-vis spectra with a detection limit of 2 and 0.18 hemagglutination units (HAU), respectively, which is comparable to the commercially available influenza colloid gold rapid diagnostic kits. These findings demonstrate the potential of the OA-AuNP for the development of novel multivalent antiviral conjugates and the diagnosis of influenza virus.
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Antivirais , Ouro , Nanotubos , Ouro/química , Nanotubos/química , Antivirais/farmacologia , Antivirais/química , Vírus da Influenza A/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Estrutura Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Testes de Sensibilidade Microbiana , Cães , Animais , Relação Dose-Resposta a Droga , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Notwithstanding that the past decade has witnessed unprecedented medical progress, gastric cancer (GC) remains a leading cause of cancer death, highlighting the need for effective prognostic markers. The Memorial Sloan Kettering Prognostic Score (MPS) has been validated as a valuable prognostic tool for patients with metastatic pancreatic adenocarcinoma (mPDAC). This study aimed to assess the prognostic value of the MPS in advanced GC. METHODS: Data from 367 patients were analyzed in the present study. The MPS for each patient was calculated based on the sum of scores based on the neutrophil-to-lymphocyte ratio and serum albumin levels. Multivariate analyses were performed to identify the independent clinicopathological parameters associated with overall survival (OS). Further subgroup analyses based on clinicopathological features were conducted. RESULTS: Patients with MPS 0 (n = 161), MPS 1 (n = 158), and MPS 2 (n = 48) exhibited significantly different OS, with a median survival duration of 20.7 (95%CI: 12.2-29.2), 14.9 (95%CI: 12.5-17.3), and 12.7 (95%CI: 9.3-16.0) months, respectively (p < 0.001). Significant differences in survival were observed among different groups of patients receiving chemotherapy (18.5 months vs. 14.7 months vs. 11.0 months, p = 0.03) or the subgroup receiving chemotherapy plus immunotherapy as first-line treatment (32.6 months vs. 17.7 months vs. 12.7 months, p = 0.02). The MPS was identified as an independent prognostic factor in multivariate analysis. During subgroup analyses, MPS-low (MPS 0) was consistently associated with a better prognosis than MPS-high (MPS 1 or 2). CONCLUSIONS: MPS is a practical, simple, and useful prognostic tool for patients with advanced GC. Further studies are warranted to validate its prognostic value in advanced GC.
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Adenocarcinoma , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Prognóstico , Adenocarcinoma/terapia , Linfócitos/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which consists of neuroendocrine and non-neuroendocrine components, is quite rare. Until now, most data on gastric MiNEN come from clinical cases, without large-scale retrospective studies or controlled clinical trials. Consequently, no consensus regarding the origin, molecular characteristics, or appropriate treatment of MiNEN has been reached so far. We conducted chemotherapy of irinotecan plus cisplatin (IP regimen) and surgery in two patients with gastric MiNEN, which had never been used in treating this kind of tumor, leading to their long-term survival for more than 3 and 7 years, respectively. CASE SUMMARY: We present two patients (one male and one female) with gastric MiNEN, with the primary manifestation of recurrent upper abdominal pain. After they were referred to our hospital, a diagnosis of gastric MiNEN was defined with the help of CT scan, and histopathological and immunohistochemical examinations on the samples of gastrointestinal endoscopy or radical surgery. The male patient (case 1) were found to have metastases in the reginal lymph nodes and the left liver. He received four cycles of IP regimens first, then the gastrectomy and partial left liver resection, followed by additional two cycles of IP chemotherapy. The female patient (case 2) underwent a laparoscopic gastrectomy, and received six cycles of IP regimen. She was found to have metastatic lesions in the right lung 2 years after that, and underwent video-assisted thoracoscopic surgery (VATS) of the lower lobe of the right lung. The two patients have now survived for more than 3 years and 7 years, respectively, without any evidence of recurrence or metastases. CONCLUSION: IP regimen, combined with curative-intent surgery if feasible, could be considered as the priority in the choice of front-line chemotherapy for gastric MiNEN.
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Therapies for patients with advanced esophageal squamous cell carcinoma (ESCC) are limited and accompanied by dismal prognosis. Here we use ESCC cell line K30 and TE-1 to investigate the antitumor efficacy of cisplatin plus anti-PD-1 antibody. Enhanced antitumor effects and increased CD8+ tumor-infiltrating lymphocytes of combination therapy were observed in TE-1 cells bearing humanized mice model. Lower cell viability and more cell apoptosis were found in the combination therapy in vitro. We next analyzed clinical data from patients with advanced ESCC received cisplatin-based chemotherapy plus an anti-PD-1 antibody (Tislelizumab or Sintilimab) as first line therapy from two clinical trials (NCT03469557, NCT03748134). With the response rate of 81.8%, duration of response of 15.2 months, median progression-free survival of 15.5 months, median overall survival of 21.5 months and manageable toxicity in patients with advanced ESCC, we demonstrated that cisplatin-based chemotherapy plus anti-PD-1 antibody is an effective and safe option. We further confirmed sublethal cisplatin could induce PD-L1 expression in ESCC cells and cisplatin-treated ESCC cells suppressed the activation and function of immune cells while the addition of sintilimab prevented this process. These results highlight the effectiveness of cisplatin combining with anti-PD-1 antibody in patients with advanced ESCC, revealed its capability to promote the PD-L1 expression in ESCC cells and act synergistically with anti-PD-1 antibody to restore exhausted immune cells activities, thus providing a theoretical basis for further explorations in the mechanism of the combination treatment of cisplatin-based chemotherapy with immune checkpoint inhibitors in ESCC.
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Background: The emergence of immune checkpoint inhibitors has changed the landscape of first-line treatment of patients with advanced gastric cancer. Currently, the prognostic significance of inflammatory markers in first-line immunotherapy combined with chemotherapy for gastric cancer is currently unclear. This study aimed to identify inflammatory markers with potential to predict treatment outcome in advanced gastric cancer patients receiving immunotherapy combined with chemotherapy. Methods: This retrospective study enrolled untreated advanced or metastatic gastric or gastro-esophageal junction cancer patients from 5 clinical trials (the clinical trial cohort) and the real world (the real-word cohort). Inflammatory markers included in the analysis included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR). Receiver operating characteristic (ROC) curves were constructed to identify optimal cut-off values. The prognostic potential of the markers was determined using Kaplan-Meier analysis, univariate and multivariate Cox-regression analyses in the clinical trial cohort and the findings were validated in the real-world cohort. Results: In the clinical trial cohort (n=45), MLR, PLR and SII were associated with PFS but not OS (All P<0.05), while dNLR was not correlated with PFS or OS. Only NLR was associated with PFS and OS and identified as an independent prognostic predictor in the univariate and multivariate analyses. The prognostic value of NLR was validated in the real-world cohort (n=55). Conclusions: NLR was a strong predictor of PFS and OS in patients with advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy. Further prospective studies are required to validate our results.
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BACKGROUND: Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy. METHODS: Data of clinical features, peripheral blood parameters, and treatment records were collected in unresectable ESCC patients who received PD-1/PD-L1 inhibitors plus chemotherapy as the first-line treatment from September 2017 to August 2021. The nomogram based on MLR and clinical parameters for predicting the overall survival (OS) was developed and validated. RESULTS: Out of 81 patients enrolled, patients with a lower MLR had significantly longer progression-free survival (PFS) and OS than patients with a higher pretreatment MLR (p = 0.0067; p = 0.00069). The OS nomogram integrating MLR, performance status (PS) score, and body mass index (BMI) achieved a C-index of 0.770 (95%CI 0.645-0.896). The area under the ROC curve (AUC) value of the nomogram predicting 12-, 18-, and 24-month OS rates were 0.855, 0.792, and 0.744, respectively, which were higher than the clinical TNM staging system or the MLR. Stratified by the nomogram-generated scores, three risk groups (low, moderate, and high) in survival curves manifested a distinct difference (p < 0.0001). CONCLUSION: MLR emerged as an independent predictive factor for PFS and OS in treatment-naive unresectable ESCC patients treated with chemoimmunotherapy. The constructed nomogram of MLR and clinical parameters was a reliable model for prognostic estimation.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Nomogramas , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Monócitos/patologia , Linfócitos/patologiaRESUMO
BACKGROUND: Sintilimab is a humanized monoclonal antibody against the programmed cell death 1 (PD-L1). We aimed to assess the safety and activity of sintilimab monotherapy or in combination with chemotherapy in advanced solid tumors. METHODS: This phase Ib study included six cohorts. Cohort A-C were sintilimab monotherapy settings, and enrolled pretreated patients (2/3 L cohorts). Cohort D-F were treatment-naïve patients (1 L cohorts), and received sintilimab plus different chemotherapies. The primary endpoints were safety and objective response rate (ORR). Exploratory endpoints were potential biomarkers for the prognosis after treatment, such as tumor mutation burden scores (TMB), PD-L1 and lymphocyte-to-monocyte ratio (LMR). RESULTS: The ORR was 14.6% in the 2/3 L cohorts (n=146), and 73.2% in the 1 L cohorts (n=61). The incidence of grade 3-4 adverse events occurred in 55 patients (37.7%) in 2/3 L cohorts, and in 38 (62.3%) in 1 L cohorts. 157 patients had available TMB scores, and in 2/3 L cohorts, patients in the high TMB groups (TMB≥10) showed a longer progression-free survival (PFS) and overall survival (OS) than those in the low TMB groups (TMB<10). No significant differences in PFS and OS were observed across different PD-L1 groups in both 1 L and 2/3 L cohorts. A high LMR was significantly associated with an improved PFS in 1 L cohorts (P=0.022). CONCLUSION: Sintilimab alone or combined with chemotherapy had a tolerable safety profile in solid tumors. The combination therapy showed a favorable activity with advanced non-small cell lung cancer and gastric or esophagogastric junction adenocarcinoma. LMR might be a prognostic factor for the combination regimen in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02937116. Registered 18 October 2016.
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Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3âweeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85âmg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120âmg/day depending on different body surface areas of <1.25âm, 1.25-1.5âm, or >1.5âm respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2âweeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/Fâ=â33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4âmonths (95% CI, 3.37-5.36âmonths) and 10.3âmonths (95% CI, 8.88-11.3âmonths), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.
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Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Intervalo Livre de Doença , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/secundário , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. METHODS: Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days. RESULTS: Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1-6) was administered. Overall response rate was 46.2% (95% confidence interval: 32-65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6-8.4 months) and 13.6 months (95% confidence interval: 10.2-17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients. CONCLUSION: The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. TRIAL REGISTRATION: ISRCTN88259320.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/patologia , Idoso , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/mortalidade , Urotélio/efeitos dos fármacos , GencitabinaRESUMO
The pivotal role of the long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in anti-cancer drug resistance has been confirmed in many cancers. Overexpression of lncRNA UCA1 correlates with resistance to chemotherapeutics such as cisplatin, gemcitabine, 5-FU, tamoxifen, imatinib and EGFR-TKIs, whereas lncRNA UCA1 knockdown restores drug sensitivity. These studies highlight the potential of lncRNA UCA1 as a diagnostic and prognostic biomarker, and a therapeutic target in malignant tumors. In this review, we address the role of lncRNA UCA1 in anti-cancer drug resistance and discuss its potential in future clinical applications.
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PURPOSE: Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer. METHODS: Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120 mg/m(2) on day 1 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle. RESULTS: Forty-four patients (M/F = 33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2 %) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6 % partial response in 17 patients, 45.4 % stable disease in 20 patients, and 13.6 % progressive disease in six patients. Thirty-four patients (77.3 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2 months (95 % CI 4.08-6.39 months) and 12.2 months (95 % CI 8.81-15.60 months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5 %), grade 3 neutropenia in 14 patients (40.9 %), and grade 4 neutropenia in four patients (9.0 %). Two patients (4.5 %) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5 % (grade 3/4, 4.5 %), 31.8, 95.4, and 18.1 % (grade 3/4, 2.2 %), respectively. CONCLUSIONS: Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Prospectivos , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Adulto JovemRESUMO
To analyze the single nucleotide polymorphisms (SNPs) of two subtypes of neurokinin (NK) receptors, NK1R and NK2R (also known as TAC1R and TAC2R), in colorectal cancer (CRC), peripheral blood samples were collected from 199 CRC patients. Direct-sequencing was performed to identify the NK1R rs10198644 and NK2R rs4644560 SNPs. Genotype results were correlated with clinical factors. The allele frequencies of NK1R rs10198644 GC, CC and GG were 52, 17 and 31%, respectively, while that of NK2R rs4644560 GC, CC, and GG were 36, 50 and 14%, respectively. Patients with NK2R rs4644560 GC exhibited more positive lymph nodes than those with CC (mean, 2.2 vs. 1.3; P=0.016). Further analysis highlighted that the number of positive lymph nodes was also increased in the NK2R rs4644560 GC/NK1R rs10198644 GG group compared with the NK2R rs4644560 GG/NK1R rs10198644 GG group (mean, 2.2 vs. 0.9; P=0.04). These data suggested that the NK2R rs4644560 GC polymorphism alone or combination with NK1R rs10198644 GG may be a promising prognostic marker of lymph node metastasis in CRC patients.
RESUMO
BACKGROUND: Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). METHODS: Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m(2) on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles). RESULTS: Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively. CONCLUSIONS: The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.
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A phase II clinical trial was performed to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small-cell lung cancer (NSCLC) patients. Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250 mg/day) between April 2002 and January 2010. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24 (60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20 months (95% CI: 11.9-28 months) and 13 months (95% CI: 8.0-17.9 months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65 years (P < 0.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%), and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC.