RESUMO
BACKGROUND: Locally advanced or metastatic adenocarcinoma of the pancreas remains - despite the implementation of new chemotherapy protocols - a disease with short overall survival (OS). METHODS: Eighty-three patients were treated with locally advanced or metastatic adenocarcinoma of the pancreas with either FOLFIRINOX or nab-Paclitxel and Gemcitabine (nabPGem) as first- or second line therapy. We analysed the outcome for OS and progression-free survival (PFS) in terms of treatment regimen and sequence. RESULTS: The majority of patients presented in good performance status (PS) with a median age of 68 years. Fourty-two patients received FOLFIRINOX as first-line therapy, 41 patients were treated with nabPGem as first line therapy. Forty-eight patients received both treatments. The OS of all 83 patients was 12.6 months (95% CI: 10.7-14.6), resulting in a 1-year OS of 54%. Forty-eight patients received FOLFIRINOX followed by nabPGem or vice versa. There was no significant difference in OS or PFS for either of the two sequences (p = 0.9). The OS for FOLFIRINOX followed by nabPGem or nabPGem followed by FOLFIRINOX was 13.7 months (95% CI: 12.6-14.7) and 13.8 months (95% CI: 8.6-19), respectively. CONCLUSIONS: The sequence FOLFIRINOX followed by nab-Paclitaxel and Gemcitabine or vice versa lead to an equal OS outcome.
Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Oxaliplatina , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: A frequent side effect of the multikinase inhibitor regorafenib is fatigue. Physical activity has shown potential in reducing cancer-related fatigue. METHODS: This non-interventional pilot study assessed physical activity levels of metastatic colorectal cancer (mCRC) patients treated with regorafenib based on median daily step counts measured at 1week intervals using a pedometer. The study further evaluated relations between physical activity levels and fatigue, quality of life (QoL) and progression-free survival. RESULTS: Pedometer data were available for 22 out of 25 enrolled patients. The numbers of days with available pedometer data ranged from 6 to 100 days. The overall median daily step count was 2357 (range 10-14,931), with substantial interindividual and intraindividual variations. Interindividual median weekly step counts were in the range of 5000-7000 in some, 2000-3000 in others, and several hundreds or less in a few patients. Intraindividual daily step counts also varied by several thousands of steps. Step counts in weeks in which patients reported fatigue were well within the range of or even higher than step counts in adjacent weeks, indicating a lack of correlation. The risk of disease progression was also independent of median weekly step counts; however, significant correlations were seen between QoL and step counts. CONCLUSION: Despite the severity of their disease patients showed remarkable levels of walking activity. In view of the highly individual activity levels, exercise prescriptions for seriously ill patient populations should be personalized to the specific needs and preferences of each individual patient.
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Neoplasias Colorretais , Qualidade de Vida , Neoplasias Colorretais/tratamento farmacológico , Exercício Físico , Humanos , Compostos de Fenilureia , Projetos Piloto , Piridinas , CaminhadaRESUMO
BACKGROUND: Ramucirumab is a VEGFR-2 antibody that has proven to prolong overall survival (OS) in patients with pretreated metastatic gastric/gastrooesophageal junction (GEJ) adenocarcinoma. We present data from patients treated with ramucirumab and paclitaxel or FOLFIRI after failure of at least one platinum- and 5-FU-containing chemotherapy (CHT) regimen. METHODS: In this retrospective two-center study, 56 patients with metastatic gastric cancer (47%) or adenocarcinoma of the GEJ (53%) were treated with paclitaxel and ramucirumab (n=38) as second-line (75%) or beyond second-line (25%) therapy. FOLFIRI-ramucirumab (FOLFIRI-R) (n=16) was given to patients with a short interval between taxane-based perioperative CHT and occurrence of metastatic disease or to those ineligible for paclitaxel. RESULTS: The median progression-free survival (PFS) and OS for patients treated with paclitaxel-ramucirumab (pacl-R) were 2.9 (95% CI: 2.3-3.6) and 4.4 (4.1-4.7) months, respectively, and those for patients treated with FOLFIRI-R were 5.9 (95% CI: 0.35-11.4) and 8.3 (6.6-10) months, respectively (P=0.05). We observed a trend towards prolonged PFS after perioperative taxane-based FLOT CHT (n=12) with FOLFIRI-R compared with pacl-R. Adverse events were manageable, with neutropenia and polyneuropathy (PNP) being the most common events. More than two treatment lines were given to 48.2% of patients. CONCLUSIONS: The use of ramucirumab in combination with FOLFIRI showed favourable PFS and OS in patients with prior treatments with platinum and/or taxane-based agents and allows further treatment lines after progression. In patients with taxane pretreatment or persistent high-grade PNP, the combination of FOLFIRI-R might be a promising combination.
RESUMO
OBJECTIVE: The role of CA 19-9 in monitoring treatment response in advanced pancreatic cancer remains uncertain. We assessed its value in predicting early failure of first-line chemotherapy. METHODS: Data of 84 patients with advanced pancreatic cancer who had received first-line chemotherapy were analyzed with regard to changes in CA 19-9 during the first 2 months of treatment. RESULTS: Median time to progression and overall survival in patients with a transient increase in CA 19-9 during month 1 (n = 15; 5.5 and 13 months) and in those with no increase during the 2 months (n = 52; 6.5 and 12 months) were comparable and slightly above the median values of the entire study population. The hazard ratios for disease progression for a 20% increase in CA 19-9 during the first and second month of therapy were 1.065 and 1.339 in the univariate- and 1.092 and 1.298 in the multiple Cox regression model, respectively. CA 19-9 did not influence survival. CONCLUSION: Our results suggest that early CA 19-9 measurements are weakly associated with disease progression rather than survival in patients with advanced pancreatic cancer receiving palliative chemotherapy. In view of a possible tumor marker flare, values after the first month of therapy must be interpreted with caution.
Assuntos
Antígeno CA-19-9/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Falha de TratamentoRESUMO
PURPOSE: To investigate the safety and efficacy of the procoagulant wound dressing Neptune Pad (Biotronik, Berlin, Germany) compared with those of conventional manual compression for access site management after peripheral percutaneous interventions. MATERIALS AND METHODS: The study was approved by the institutional ethics committee, and all patients gave written informed consent. Two hundred one consecutive patients were enrolled and were randomly assigned to be treated with the Neptune Pad (n = 100) or conventional manual compression (n = 101). Patients were followed up clinically until hospital discharge and with duplex ultrasonography at 24 hours after the procedure to evaluate occurrence of access site complications. Time to hemostasis and time to ambulation were recorded, and patient and physician discomfort were measured by using a visual analogue scale. RESULTS: The risk for access site complications was not significantly different between the Neptune Pad group and the conventional compression group (adjusted odds ratio, 1.15; 95% confidence interval: 0.47, 2.84; P = .76). Time to hemostasis was marginally reduced in the Neptune Pad group. Patient and physician discomfort were lessened with use of the device. CONCLUSION: The hemostatic device Neptune Pad does not improve the safety of access site management after peripheral percutaneous procedures. Markedly improved comfort was noted among patients in the Neptune Pad group and by the physicians obtaining hemostasis.
Assuntos
Angioplastia com Balão , Bandagens , Técnicas Hemostáticas/instrumentação , Idoso , Idoso de 80 Anos ou mais , Alginatos/administração & dosagem , Feminino , Ácido Glucurônico/administração & dosagem , Ácidos Hexurônicos/administração & dosagem , Humanos , Masculino , Pacientes , Pressão , Doenças Vasculares/cirurgiaRESUMO
Antisense oligonucleotides have recently been identified as new anticancer agents. Since human head and neck cancer cells highly express the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1), the aim of this study was to explore the efficacy of the Mcl-1 suppression in combination with various cytotoxic agents in the head and neck cancer cell line SCC9. After oligonucleotide transfection and/or treatment with cisplatin, 5-fluorouracil (5-FU), gemcitabine, paclitaxel or cetuximab, proliferation assays were performed to determine cell viability. The expression patterns of Mcl-1, Bax and Bak were assessed by Western blot analysis and the apoptotic cells were determined by immunohistochemistry using the M30 antibody. A combined Mcl-1 antisense oligonucleotide treatment with paclitaxel, cetuximab and gemcitabine led to a significant reduction in the viable cells. However, the combination with cisplatin and 5-FU showed only moderate synergistic cytotoxic effects. According to the cytotoxic data, distinct apoptosis rates were observed after the combined treatment with the different substances. Western blot analysis also showed a significant suppression of the Mcl-1 synthesis. Our data show that the Mcl-1 antisense oligonucleotide in combination with certain cytotoxic agents has the potential to significantly decrease cell viability in vitro.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Apoptose/fisiologia , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cetuximab , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Regulação para Baixo , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Técnicas Imunoenzimáticas , Proteína de Sequência 1 de Leucemia de Células Mieloides , Oligonucleotídeos Antissenso/farmacologia , Paclitaxel/administração & dosagem , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Tumorais Cultivadas , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , GencitabinaRESUMO
BACKGROUND: To compare safety, visual acuity (VA), and anatomic outcomes of 2.5 mg/kg and 5 mg/kg intravenous bevacizumab in patients with neovascular age-related macular degeneration. METHODS: In an institutional cohort study, 16 patients (2 cohorts, 27 eyes) with neovascular age-related macular degeneration were treated with 5 mg/kg intravenous bevacizumab and 2.5 mg/kg, respectively. All patients received 3 initial intravenous infusions at 2-week intervals. The main outcome measures were VA, optical coherence tomography, and fluorescein angiography. RESULTS: No serious systemic or ocular adverse events were identified. By Day 7, mean VA increased from 56 letters (20/80(+1)) at baseline to 60 letters (20/63) in the 5 mg/kg group and mean central retinal thickness decreased by 83 microm. In the 2.5 mg/kg group, mean VA increased from 55 letters (20/80) to 66 letters (20/50(+1)) and mean central retinal thickness decreased by 93 microm. By Month 3, VA improved by 10 letters compared to baseline in the 5 mg/kg group and by 9 letters in the 2.5 mg/kg group. Central retinal thickness was reduced by 128 microm in the 5 mg/kg group and by 127 microm in the 2.5 mg/kg group. These benefits were sustained through 6 months. No statistically significant difference was found between both treatment groups regarding safety, VA, and anatomic outcomes. CONCLUSION: Similar VA, optical coherence tomography, and angiographic improvements were observed in both treatment groups up to 6 months. Further follow-up is required to evaluate the long-term durability and safety of both treatment regimens.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Bevacizumab , Pressão Sanguínea , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Humanos , Infusões Intravenosas , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to induce apoptosis in various cell lines. So far, the molecular targets that account for this effect are unknown. Akt and extracellular-signal regulated kinase (ERK) are both important signaling molecules, which promote survival in different types of cancer, including head and neck cancer. The aim of our study was to describe the effect of treatment with nimesulide and ERK inhibitor PD 98059 on the expression patterns of Akt within the head and neck cancer cell lines SCC 9 and SCC 25. SCC 9 and SCC 25 cells were cultured in RPMI and treated with nimesulide and PD 98059. Protein expression levels were semi-quantified by Western blot analysis. Apoptosis was examined using the M30 antibody that binds to a caspase cleaved cytoskeletal protein for detection of early apoptosis in immunofluorescence studies. In both cell lines, nimesulide treatment induced apoptosis and resulted in a decrease of Akt expression. ERK inhibition had no effect on Akt expression, and combined application of both agents had the same effect as treatment with nimesulide alone. In conclusion, nimesulide induces apoptosis and promotes down-regulation of Akt-expression in squamous cell carcinoma cells, independently of ERK activity.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Sulfonamidas/farmacologia , Apoptose , Carcinoma de Células Escamosas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt , Células Tumorais CultivadasRESUMO
Betulinic acid (BetA), a new experimental cytotoxic compound that is active against human melanoma cells and neuroectodermal tumor cells, has recently been shown to be also effective against head and neck squamous carcinoma cells (HNSCC). In this study we investigated BetA in combination with cisplatin in squamous cell carcinoma cell lines of the tongue. SCC25 and SCC9 were treated with BetA and/or cisplatin. Cells were counted with an automated analyzing system. Caspase activation was determined using the M30 Cyto-Death ELISA, expression of the anti-apoptotic protein Mcl-1 by Western blot analysis. Visualization of apoptotic cells was achieved by immunohistochemistry. Synergistic cytotoxic effect and the induction of apoptosis under combined treatment was observed in SCC25 cells only after 24 or 48 h, whereas treatment of SCC25 cells for 72 h with BetA and cisplatin showed antagonism or subadditive effects. In SCC9 cells, antagonism occurred over an increase of dose and time during treatment. Furthermore, we could not demonstrate a significant alteration in the expression of the anti-apoptotic protein, Mcl-1. Our in vitro data demonstrate that BetA seems to be an unlikely candidate for combination with cisplatin in the treatment of head and neck cancer.
Assuntos
Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Triterpenos/farmacologia , Antineoplásicos/farmacologia , Apoptose/genética , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas de Neoplasias/metabolismo , Triterpenos Pentacíclicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Ácido BetulínicoAssuntos
Infecções por Vírus Epstein-Barr/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Língua/microbiologia , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/patologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Doenças da Língua/tratamento farmacológico , Doenças da Língua/patologia , Resultado do Tratamento , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêuticoRESUMO
BACKGROUND: Our aim in this study was to identify prognostic factors and the optimal therapeutic management in patients with minor salivary gland carcinomas. METHODS: Overall and disease-free survival and overall survival after recurrence in patients with adenoidcystic carcinoma (n = 25), mucoepidermoid carcinoma (n = 8), adenocarcinoma (n = 5), carcinoma ex pleomorphic adenoma (n = 4), and others (n = 5) were correlated to clinical data. RESULTS: Overall survival correlated to treatment modality (p = .039) and T classification (p = .003), whereas prolonged disease-free interval correlated to treatment (p < .001) and T classification (p = .009). Overall survival after recurrence correlated to treatment of recurrence (p = .006) and initial T classification (p = .02). Multivariate analysis showed that overall survival after recurrence correlated to treatment of recurrence (p = .019) and initial T classification (p = 0.019). T classification was a prognostic factor for overall survival (p = .002) and disease-free interval (p = .002). CONCLUSIONS: The initial tumor classification is a clinical predictor for patients' overall and disease-free survival and overall survival after recurrence. Multimodal treatment significantly improves patients' overall survival.
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Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/terapia , Glândulas Salivares Menores/patologia , Adenoma Pleomorfo/mortalidade , Adenoma Pleomorfo/patologia , Adenoma Pleomorfo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/terapia , Carcinoma Mucoepidermoide/mortalidade , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/terapia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/cirurgia , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether treatment with 7beta-hydroxycholesterol (7beta-HC) would trigger cell death in head and neck squamous cell carcinoma (HNSCC) cell lines in a dose-dependent fashion. DESIGN: In vitro study. SUBJECTS: The study included HNSCC cell lines SCC9, SCC25, CAL27, and FaDu. INTERVENTION: We treated HNSCC cell lines with increasing doses of 7beta-HC. Proliferation assays were performed to assess cell viability after treatment. Western blots were carried out to evaluate cyclooxygenase (COX)-1 and -2 expression levels. RESULTS: Using proliferation assays and immunocytochemical analysis, we detected significant growth inhibition via apoptosis in 4 different HNSCC cell lines after treatment with 7beta-HC (P < .001). The 50% inhibitory concentration levels were between 13.19 and 20.79 micromol/L after 72 hours. Western analysis indicated that COX-2, but not COX-1, levels were suppressed after treatment. CONCLUSIONS: Treatment with 7beta-HC resulted in suppression of HNSCC growth in vitro. Our data warrant further investigations for the potential use of 7beta-HC as a cytotoxic agent in head and neck cancer.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/enzimologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias de Cabeça e Pescoço/enzimologia , Hidroxicolesteróis/farmacologia , Western Blotting , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-HistoquímicaRESUMO
PURPOSE: This study was conducted to determine the expression of Bmi-1 and podoplanin in healthy oral mucosa and in untreated tumor tissues samples of patients with squamous cell carcinomas of the head and neck. All patients were treated by primary radio(chemo)therapy. METHODS AND MATERIALS: The expression of Bmi-1 and podoplanin was immunohistochemically evaluated in 12 normal oral mucosa and 63 tumor specimens and correlated with patients' clinical data. RESULTS: In healthy mucosa expression of Bmi-1 and podoplanin was restricted to the basal cell layer. Expression of both proteins was found in 79% and 86% of our tumor samples, respectively. In 17 and 8 samples, Bmi-1 and podoplanin were co-expressed at the invasive border or diffuse in the bulk of the tumor, respectively. Univariate analysis showed that the co-expression of Bmi-1 and podoplanin correlated to decreased overall survival (p = 0.044). Moreover, multivariate testing identified high expression of podoplanin (p = 0.044), co-expression of Bmi-1 and podoplanin (p = 0.007) and lack of response to therapy (p < 0.0001) as predictors of shortened overall survival in patients treated with primary radio(chemo)therapy. CONCLUSIONS: Bmi-1 and podoplanin are expressed at the invasive front of squamous cell carcinomas of the head and neck. Co-expression of Bmi-1 and podoplanin predicts significantly overall survival of patients treated with primary radio(chemo)therapy.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Complexo Repressor Polycomb 1 , Prognóstico , Dosagem Radioterapêutica , Análise de SobrevidaRESUMO
OBJECTIVE: Metastasis to the jaw is a rare finding in pancreatic cancer; only five cases of tumor spread to the oral region have been described. CASE REPORT: We report on a previously healthy 54-year-old man who attended the hospital in 2006 because of a mandibular mass. Histology was positive for adenocarcinoma and computed tomography led to the diagnosis of pancreatic cancer. Chemoradiotherapy was started but had to be stopped early because of intraoral bleeding from the metastasis. The patient subsequently received palliative chemotherapy. The primary cancer was stabilized but the mandibular mass progressed despite cytostatic therapy. Despite best supportive measures the patient died nine months after presentation. CONCLUSION: In making the decision on whether metastasectomy should be performed in an uncommon site of metastatic spread such as the mandibula, both the possibility of cure and also the potentially decreased response to conservative therapy and the patient's decreased quality of life have to be considered.
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Adenocarcinoma/etiologia , Adenocarcinoma/secundário , Edema/etiologia , Neoplasias Mandibulares/complicações , Neoplasias Mandibulares/secundário , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia , Adenocarcinoma/terapia , Edema/diagnóstico , Face , Humanos , Masculino , Neoplasias Mandibulares/terapia , Pessoa de Meia-IdadeRESUMO
Active anticancer drugs and/or combination regimens for the treatment of patients failing oxaliplatin, irinotecan and 5-fluorouracil are desperately needed. In this analysis we describe the safety and efficacy of the combination of mitomycin C, UFT and leucovorin in such an extensively pretreated patient population. Between January 2002 and June 2004, a total of 41 patients were treated with mitomycin C (8 mg/m on day 1) and UFT (350 mg/m)+ leucovorin (90 mg) both divided into three daily doses from day 1 to day 14 every 4 weeks. All patients had failed prior first-line and second-line treatment with oxaliplatin, irinotecan and 5-fluorouracil. The aim of this retrospective analysis was to evaluate the efficacy and safety data of this potential salvage therapy regimen. Thirty-nine patients were evaluable for the response. The overall response rate (intent-to-treat) was 7.3% (95% confidence interval, 2.5-19.4%) and disease stabilization was achieved in 29.3%. Median time to progression was 2.5 months (range, 1.5-13.5) and median overall survival was 6 months (range, 1.5-26). Myelosuppression was the most frequent side effect. Grade 3 hematotoxicity, however, was observed in only three patients. The most common nonhematological toxicities consisted of mild and reversible nausea, emesis and diarrhea; again, severe symptoms were only occasionally seen. These data show that the combination of mitomycin C/UFT/leucovorin is safe and active in about one-third of patients in terms of abrogation of progression in extensively pretreated metastatic colorectal cancer.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Terapia de Salvação , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Mitomicina/uso terapêutico , Metástase Neoplásica , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/uso terapêutico , Uracila/administração & dosagem , Uracila/efeitos adversos , Uracila/uso terapêuticoRESUMO
A phase II trial was performed to investigate the efficacy and tolerance of combined gemcitabine and liposomal doxorubicin +/- recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapeutically pretreated metastatic breast cancer. Thirty-four patients were entered in this trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin +/- G-CSF. Twenty seven patients received this regimen as 2nd line therapy, five patients as 3rd line and two patients as 4th line therapy after having failed taxane- and/or anthracycline-based chemotherapy or other drug combinations. After a median of six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was observed; 14 patients had disease stabilization (41%), and eight (24%) progressed. Three patients were not evaluable for response due to anaphylaxis after the first course and protracted thrombocytopenia. The median TTP was 7.5 months, and median overall survival was 15 months. Myelosuppression was the most frequently observed toxicity. Non-haematological side effects were generally mild to moderate. Our data suggest that gemcitabine and liposomal doxorubicin +/- G-CSF is an effective and fairly well tolerated regimen for chemotherapeutically pretreated patients with advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Doxorrubicina/análogos & derivados , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: The protooncogenes Ets-1 and Ets-2 are involved in carcinogenesis of different tumors. Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, has antiproliferative effects on tumor cells. The question arises whether nimesulide influences Ets-1 and Ets-2 synthesis in head and neck tumors. METHODS: Expression of Ets-1 and Ets-2 was analyzed in tumor tissues by immunohistochemistry. The influence of nimesulide and an extracellular signal-regulated kinase (ERK) inhibitor on cell proliferation of two head and neck cancer cell lines and Ets-1 and Ets-2 expression was determined by automated cell counting and Western blotting, respectively. RESULTS: Immunohistochemistry showed a high expression of Ets-1 and Ets-2 in tumor tissues. In both cell lines, Ets-1 and Ets-2 expression were reduced after 24 and 48 hours by nimesulide. CONCLUSION: Both Ets-1 and Ets-2 are overexpressed in head and neck cancer specimens. Inhibition of Ets-1 and Ets-2 expression in head and neck cancer cell lines by nimesulide might explain the proapoptotic property of this COX-2 inhibitor.