RESUMEN
Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Exantema/terapia , Crema para la Piel/uso terapéutico , Piel/efectos de los fármacos , Bevacizumab/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias Colorrectales/patología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
miR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation and cancer. We hypothesized that miR-296-5p is involved in breast cancer onset and progression possibly through regulation of its target SCRIB (Scribble), a polarity protein recently implicated in the acquisition of cancer stem cell traits and in cell motility. We found that miR-296-5p levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma, and low expression of this miRNA predicted shorter disease-free survival independently of classic clinicopathological parameters. Further, reduced miR-296-5p levels were significantly correlated with an earlier spread of cancer in the overall series and with distant metastases in the subset. In contrast with its regulator, SCRIB was overexpressed and mislocalized in primary breast cancers or locoregional or distant metastatic lesions compared with normal parenchyma. Notably, SCRIB mislocalization was associated with overall survival, metastatic spread and organ tropism in patients with breast cancer. Finally, direct injection of a precursor miR-296-5p into tumours of a breast cancer xenograft model significantly decreased tumour growth. Our results show that the miR-296-5p/SCRIB axis plays a role in breast carcinogenesis and an miR-296-5p-based therapeutic approach hampers breast cancer tumour growth in vivo. Modulation of miR-296-5p may represent a new therapeutic option for patients with breast cancer.
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Neoplasias de la Mama/genética , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Diferenciación Celular/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , MicroARNs/genética , Persona de Mediana Edad , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Previous trials have shown that anti-EGFR monoclonal antibodies can improve clinical outcomes of patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SCCHN). We assessed the efficacy and safety of panitumumab combined with cisplatin and fluorouracil as first-line treatment for these patients. METHODS: This open-label phase 3 randomised trial was done at 126 sites in 26 countries. Eligible patients were aged at least 18 years; had histologically or cytologically confirmed SCCHN; had distant metastatic or locoregionally recurrent disease, or both, that was deemed to be incurable by surgery or radiotherapy; had an Eastern Cooperative Oncology Group performance status of 1 or less; and had adequate haematological, renal, hepatic, and cardiac function. Patients were randomly assigned according to a computer-generated randomisation sequence (1:1; stratified by previous treatment, primary tumour site, and performance status) to one of two groups. Patients in both groups received up to six 3-week cycles of intravenous cisplatin (100 mg/m(2) on day 1 of each cycle) and fluorouracil (1000 mg/m(2) on days 1-4 of each cycle); those in the experimental group also received intravenous panitumumab (9 mg/kg on day 1 of each cycle). Patients in the experimental group could choose to continue maintenance panitumumab every 3 weeks. The primary endpoint was overall survival and was analysed by intention to treat. In a prospectively defined retrospective analysis, we assessed tumour human papillomavirus (HPV) status as a potential predictive biomarker of outcomes with a validated p16-INK4A (henceforth, p16) immunohistochemical assay. Patients and investigators were aware of group assignment; study statisticians were masked until primary analysis; and the central laboratory assessing p16 status was masked to identification of patients and treatment. This trial is registered with ClinicalTrials.gov, number NCT00460265. FINDINGS: Between May 15, 2007, and March 10, 2009, we randomly assigned 657 patients: 327 to the panitumumab group and 330 to the control group. Median overall survival was 11·1 months (95% CI 9·8-12·2) in the panitumumab group and 9·0 months (8·1-11·2) in the control group (hazard ratio [HR] 0·873, 95% CI 0·729-1·046; p=0·1403). Median progression-free survival was 5·8 months (95% CI 5·6-6·6) in the panitumumab group and 4·6 months (4·1-5·4) in the control group (HR 0·780, 95% CI 0·659-0·922; p=0·0036). Several grade 3 or 4 adverse events were more frequent in the panitumumab group than in the control group: skin or eye toxicity (62 [19%] of 325 included in safety analyses vs six [2%] of 325), diarrhoea (15 [5%] vs four [1%]), hypomagnesaemia (40 [12%] vs 12 [4%]), hypokalaemia (33 [10%] vs 23 [7%]), and dehydration (16 [5%] vs seven [2%]). Treatment-related deaths occurred in 14 patients (4%) in the panitumumab group and eight (2%) in the control group. Five (2%) of the fatal adverse events in the panitumumab group were attributed to the experimental agent. We had appropriate samples to assess p16 status for 443 (67%) patients, of whom 99 (22%) were p16 positive. Median overall survival in patients with p16-negative tumours was longer in the panitumumab group than in the control group (11·7 months [95% CI 9·7-13·7] vs 8·6 months [6·9-11·1]; HR 0·73 [95% CI 0·58-0·93]; p=0·0115), but this difference was not shown for p16-positive patients (11·0 months [7·3-12·9] vs 12·6 months [7·7-17·4]; 1·00 [0·62-1·61]; p=0·998). In the control group, p16-positive patients had numerically, but not statistically, longer overall survival than did p16-negative patients (HR 0·70 [95% CI 0·47-1·04]). INTERPRETATION: Although the addition of panitumumab to chemotherapy did not improve overall survival in an unselected population of patients with recurrent or metastatic SCCHN, it improved progression-free survival and had an acceptable toxicity profile. p16 status could be a prognostic and predictive marker in patients treated with panitumumab and chemotherapy. Prospective assessment will be necessary to validate our biomarker findings. FUNDING: Amgen Inc.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Asia , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/virología , Cisplatino/administración & dosificación , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/química , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/química , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/virología , América del Norte , Panitumumab , Papillomaviridae/aislamiento & purificación , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Retrospectivos , América del Sur , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated. METHODS: Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated. RESULTS: The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%). CONCLUSIONS: Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/farmacocinética , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/farmacocinética , SorafenibRESUMEN
BACKGROUND: Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. METHODS: We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. CONCLUSIONS: The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases.
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Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/diagnóstico , Carga Viral , Población Blanca , Adulto , Carcinoma , ADN Viral/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/virología , Estadificación de Neoplasias , Pronóstico , RecurrenciaRESUMEN
The aim of this study was to investigate the activity and safety of a regimen containing carboplatin and paclitaxel in patients affected by recurrent or metastatic head and neck cancer. Eligible patients were treated with a 3-week combination of paclitaxel 175 mg/m2 and carboplatin area under the concentration time curve 5 mg/ml/min for a maximum of four cycles. A total of 27 patients entered the study. One patient (3.7%) had a complete response, whereas six patients (22.2%) obtained a partial response. Stable disease was observed in seven patients (25.9%). The disease control rate was 51.8% (95% confidence interval: 32.0-71.3), whereas overall response rate was 25.9% (95% confidence interval: 11.1-46.3). The median overall survival was 8.0 months (range: 2-27), with a 1-year survival of 30.5%. The median progression-free survival was 1.0 month (range: 0-14). Treatment-related deaths or episodes of neutropenic fever were not registered. Grades 3-4 neutropenia was observed in two patients (7.4%), grades 3-4 anaemia and thrombocytopenia in four (14.8%) and one (3.7%) patients, respectively. Nine patients (33.3%) experienced grades 1-2 and one patient (3.7%) grade 3 peripheral neuropathy. The combination of carboplatin and paclitaxel is safe and moderately effective for the treatment of recurrent or metastatic head and neck cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Células Escamosas/secundario , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/patología , Enfermedades Hematológicas/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Inducción de Remisión , Resultado del TratamientoRESUMEN
A Rhodococcus equi pulmonary infection in a 63-year-old man receiving chemotherapy and radiotherapy for spinocellular carcinoma is described. The patient, a knife-grinder, was promptly treated with levofloxacin plus amikacin followed by rifampicin for 2 months, and he is still in good clinical condition after an 8-month follow-up.
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Infecciones por Actinomycetales/etiología , Carcinoma de Células Escamosas/complicaciones , Neoplasias Primarias Desconocidas/complicaciones , Rhodococcus equi , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Oropharyngeal cancer is frequently associated with human papilloma virus, that also represents a strong prognostic factor. Local relaps and treatment-related complications are frequent, whereas distant metastases occur in about 25% of patients. CASE PRESENTATION: A 49 years-old male presented with a loco-regionally advanced oropharyngeal squamous cell carcinoma and was treated with concomitant chemoradiation. A complete clinical and pathological response was achieved, but the occurrence of necrotising tracheo-esophagitis, with tracheo-mediastino-pleural fistula formation, further complicated the subsequent clinical course. The patient died suddenly. Autopsy revealed multiple myocardial and epicardial metastases from oropharyngeal squamous cell carcinoma. CONCLUSIONS: Even in case of a transient complete local response, the potential occurrence of severe complications and distant metastases, although infrequent, should be considered. Cardiac metastases are frequently underestimated, as they are often asymptomatic, but may lead to sudden death. Further efforts are needed to improve diagnosis and therapy in this setting.
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OBJECTIVE: Some parameters of the Comprehensive Geriatric Assessment (CGA) are predictive of chemotherapy toxicity. The Vulnerable Elders Survey-13 (VES-13) is a short instrument that has been tested as a means of identifying patients who need a full CGA, but its ability to predict chemotherapy toxicity is still unclear. We performed a pooled analysis of four published clinical trials studying VES-13 as a means of diagnosing vulnerability, in order to evaluate its accuracy in predicting the risk of grade 3/4 toxicity in older patients undergoing chemotherapy. MATERIALS AND METHODS: The study involved patients aged ≥ 66 years with a diagnosis of solid or hematological cancer, all of whom were administered VES-13. The number of medications taken by each patient, their comorbidities, their Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score and index, the type of chemotherapy and treatment line, and their Mini Mental State Evaluation (MMSE), and Mini Nutritional Assessment (MNA) scores were recorded. Information was available concerning the grades 3-4 hematological and non-hematological toxicities experienced by each patient. RESULTS: The study involved 648 patients aged ≥ 66 years (mean age 76.2±4.5, range 66-90) of whom 336 (51.9%) were female. VES-13 identified 287 patients (44.3%) as vulnerable. Grades 3-4 hematological and non-hematological toxicities were more prevalent in the vulnerable subjects (35.2% vs 20.8%, p<0.0001, and 18.5% vs 10.8%, p=0.0055), who were also at higher risk of both (adjusted ORs 2.15, 95% CI 1.46-3.17, p<0.001); and 1.66 (95% CI 1.02-2.72, p=0.043). CONCLUSIONS: VES-13 could be considered to be a good candidate for future prospective studies to assess older patients with cancer at risk of toxicity.
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Antineoplásicos/efectos adversos , Evaluación Geriátrica/métodos , Encuestas Epidemiológicas/métodos , Neoplasias/radioterapia , Anciano , Anciano de 80 o más Años , Femenino , Evaluación Geriátrica/estadística & datos numéricos , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the fourth decade of life which account for 6 % of all osteosarcomas. This study evaluated the efficacy on the patients outcome of multimodality treatment consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients affected by jaw osteosarcoma treated with a combination of surgery, poly-chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response rate, progression-free survival and overall survival were evaluated. Neoadjuvant chemotherapy resulted in an overall response rate of 83.3 %, necrosis of grade I or II was obtained, respectively, in 44.4 and 55.6 % of the patients, and surgery was radical in all patients. At a median follow-up of 60 months, the 5-year progression-free survival and overall survival were 73.5 and 77.4 %, respectively. These outcome parameters significantly correlated with age at diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality approach including chemotherapy and radiotherapy, along with radical surgery, can maximize the outcome of patients affected by osteosarcoma of the jaws.
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Neoplasias Maxilomandibulares/epidemiología , Neoplasias Maxilomandibulares/terapia , Osteosarcoma/epidemiología , Osteosarcoma/terapia , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Quimioradioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Procedimientos de Cirugía Plástica , Estudios Retrospectivos , Adulto JovenRESUMEN
Over 1.5 years continuous piloting of a municipal wastewater plant upgraded with a double membrane system (ca. 0.6 m(3) d(-1) of product water produced) have demonstrated the feasibility of achieving high water quality with a water yield of 90% by combining a membrane bioreactor (MBR) with a submerged ultrafiltration membrane followed by a reverse osmosis membrane (RO). The novelty of the proposed treatment scheme consists of the appropriate conditioning of MBR effluent prior to the RO and in recycling the RO concentrates back to the biological unit. All the 15 pharmaceuticals measured in the influent municipal sewage were retained below 100 ng L(-1), a proposed quality parameter, and mostly below detection limits of 10 ng L(-1). The mass balance of the micropollutants shows that these are either degraded or discharged with the excess concentrate, while only minor quantities were found in the excess sludge. The micropollutant load in the concentrate can be significantly reduced by ozonation. A low treated water salinity (<10 mM inorganic salts; 280 ± 70 µS cm(-1)) also confirms that the resulting product has a high water quality. Solids precipitation and inorganic scaling are effectively mitigated by lowering the pH in the RO feed water with CO(2) conditioning, while the concentrate from the RO is recycled to the biological unit where CO(2) is stripped by aeration. This causes precipitation to occur in the bioreactor bulk, where it is much less of a process issue. SiO(2) is the sole exception. Equilibrium modeling of precipitation reactions confirms the effectiveness of this scaling-mitigation approach for CaCO(3) precipitation, calcium phosphate and sulfate minerals.
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Reactores Biológicos , Dióxido de Carbono/química , Membranas Artificiales , Ósmosis , Reciclaje/métodos , Purificación del Agua/instrumentación , Agua/química , Precipitación Química , Ciudades , Estudios de Factibilidad , Ozono/química , Permeabilidad , Sales (Química)/química , Espectrometría por Rayos X , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
PURPOSE: Radiochemotherapy of head and neck cancer causes severe mucositis in most patients. We investigated whether palifermin reduces this debilitating sequela. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received 60 or 66 Gy after complete (R0) or incomplete resection (R1), respectively, at 2 Gy/fraction and five fractions per week. Cisplatin 100 mg/m(2) was administered on days 1 and 22 (and on day 43 with R1). Patients were randomly assigned to receive weekly palifermin 120 µg/kg or placebo from 3 days before and continuing throughout radiochemotherapy. Trained evaluators performed oral assessments twice weekly. The primary end point was the incidence of severe oral mucositis (WHO grades 3 to 4). Overall survival and time to locoregional progression were also assessed. Analysis was by intention to treat. RESULTS: Severe oral mucositis was seen in 47 (51%) of 92 patients administered palifermin and 63 (67%) of 94 administered placebo (P = .027). Palifermin decreased the duration (median, 4.5 v 22.0 days) and prolonged the time to develop (median, 45 v 32 days) severe mucositis. Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms. After median follow-up of 32.8 months, 23 deaths (25%) had occurred in both treatment arms, and disease had recurred in 25 (27%) and 22 (24%) of palifermin- and placebo-treated patients, respectively. CONCLUSION: Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Factor 7 de Crecimiento de Fibroblastos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Estomatitis/prevención & control , Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante/efectos adversos , Cisplatino/efectos adversos , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Factor 7 de Crecimiento de Fibroblastos/efectos adversos , Neoplasias de Cabeza y Cuello/patología , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estomatitis/etiología , Análisis de SupervivenciaRESUMEN
PURPOSE Comprehensive geriatric assessment (CGA) is a multidimensional method used by geriatricians and oncologists to detect and evaluate multiple age-related problems and to plan and coordinate interventions. Because its main drawback is the time required, efforts have been made to evaluate screening instruments suitable for preliminarily assessing elderly patients. The main aim of this study was to establish the accuracy of the Vulnerable Elders Survey-13 (VES-13) in predicting the presence of abnormalities revealed by CGA. PATIENTS AND METHODS Patients age > or = 70 years with a histologically or cytologically confirmed diagnosis of a solid or hematologic tumor underwent both CGA and a VES-13 assessment, and the reliability and validity of VES-13 were analyzed. Results Fifty-three percent of the 419 elderly patients with cancer (mean age, 76.8 years) were vulnerable on VES-13; the rates of disabilities on CGA and activities of daily living (ADLs)/instrumental activities of daily living (IADLs) scales were 30% and 25%, respectively. The sensitivity and specificity of VES-13 were 87% and 62%, respectively, versus CGA and 90% and 70%, respectively, versus ADL/IADL scales. CONCLUSIONS On the basis of our data, VES-13 is highly predictive of impaired functional status and can thus be considered a useful preliminary means of assessing older patients with cancer before undertaking a full CGA.
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Actividades Cotidianas , Evaluación de la Discapacidad , Evaluación Geriátrica , Servicios de Salud para Ancianos , Neoplasias/diagnóstico , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Encuestas de Atención de la Salud , Humanos , Italia/epidemiología , Masculino , Neoplasias/fisiopatología , Neoplasias/psicología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The efficacy of traditional chemotherapy in inducing objective responses and prolonging survival in recurrent or metastatic head and neck cancer has been disappointing. More recent drugs have not proven superior to the classic regimen of cisplatin and 5-fluorouracil. Anti-EGFR monoclonal antibodies, either as single agents or associated to chemotherapy, have been shown to be active and little toxic. Among them, cetuximab has proven to be the most promising. Indeed the Extreme study, which compared the classic couple cisplatin (CDDP) + 5-fluorouracil with the same regimen plus cetuximab, has constituted a remarkable innovation. The results of that trial seem to indicate a third agent added to CDDP and 5-fluorouracil improved both progression-free survival and overall survival in the recurrent or metastatic setting. Unfortunately, the results obtained with the tyrosine kinase inhibitors are less impressive, and additional studies are needed to explore the potentiality of this class of drug. As far as antiangiogenetics are concerned, the research is insufficient for any conclusion to be drawn in terms of efficacy. It is hoped that, in the near future, the most active combination between biological agents and traditional chemotherapy will be found, so that the path successfully taken in other neoplastic diseases may be retraced.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de Cabeza y Cuello/patología , Humanos , RecurrenciaRESUMEN
The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.
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OBJECTIVES: Functional dependence is a costly manifestation of aging that compromises the quality of life of elderly individuals and their caregivers. In this study, we hypothesized that fatigue may be a cause of functional dependence in older cancer patients. To establish whether fatigue was associated with dependence in 1 or more activities of daily living (ADLs) or instrumental activities of daily living (IADLs), and declining performance status (PS). In addition, we studied the prevalence of fatigue and its correlation with anemia, depression, and nutritional status. MATERIALS AND METHODS: Retrospective cross-sectional study of 214 patients aged 70 and older were seen over a 3-month period by the Senior Adult Oncology Program of the H. Lee Moffitt Cancer Center in Tampa, FL. Each patient was screened with a questionnaire assessing ADLs, IADLs, PS, cognitive impairment, depression, and malnutrition. In addition, each patient underwent assessment of fatigue with the fatigue symptom inventory and a determination of complete blood counts and complete chemical panel. RESULTS: Fatigue was reported by 81% of the patients. The interference score of fatigue seemed to be a mediator for dependencies in ADLs and IADLs (P < 0.001 and 0.001), and poorer PS (P < 0.001). CONCLUSIONS: Fatigue is a common chronic problem for older cancer patients and may represent a major cause of functional dependence.
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Actividades Cotidianas , Anemia/fisiopatología , Depresión/fisiopatología , Fatiga/fisiopatología , Neoplasias/fisiopatología , Anciano , Comorbilidad , Estudios Transversales , Femenino , Evaluación Geriátrica , Hemoglobinas/análisis , Humanos , Estado de Ejecución de Karnofsky , Recuento de Linfocitos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Prevalencia , Calidad de Vida , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Prognosis of advanced hepatocellular carcinoma is dismal when locoregional treatments have failed. Systemic chemotherapy is seldom effective in inducing objective response and prolonging survival. We report a case of complete pathological remission of hepatocellular carcinoma after three cycles of systemic chemotherapy. A 64-year-old woman presented with histologically documented hepatocellular carcinoma without associated liver disease, relapsed after earlier locoregional therapy. Surgery was not performed as thoracic computerized tomography (CT) demonstrated pulmonary bilateral nodules. The patient was treated with chemotherapy consisting of three cycles of epirubicin, cisplatin, and infusional 5-fluorouracil (ECF regimen); stable lung disease and a good partial response in the liver were obtained as documented by CT scan. Hepatic segmentectomy was therefore performed and the histologic examination revealed necrosis without evidence of residual disease. Two more cycles of adjuvant chemotherapy were infused after surgery. At 1-year follow-up the patient is alive and free of disease according to a positron emission tomography/CT scan. It is suggested that an aggressive regimen like ECF should be considered in fit patients who are not affected by concomitant liver disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Pruebas de Función Hepática , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , alfa-Fetoproteínas/metabolismoRESUMEN
BACKGROUND: Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients. METHODS: From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided. RESULTS: The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm. CONCLUSIONS: Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias Gástricas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
Gemcitabine is a purine analog with known activity in many solid tumors, namely lung, breast, pancreatic, genitourinary and head/neck cancers. Cardiac toxicity is a rare event and only one report previously described atrial fibrillation (AF) as a consequence of gemcitabine infusion. We report two cases of women suffering from lung cancer who were treated with gemcitabine. Both patients were admitted to hospital for paroxysmal AF occurring 12-24 h after the infusion of the drug. In the first case a sinus rhythm was spontaneously repristinated when AF occurred for the first time, while the second episode required an anti-arrhythmic drug to interrupt the dysrhythmia. In the second case, the patient had to be treated with digitalis glycoside to control the ventricular response without attaining a sinus rhythm. We could not recognize any other precipitating factor beyond the infusion of gemcitabine as a cause for the arrhythmia. Both cases were treated with gemcitabine for lung cancer and we observed the appearance of AF less than 24 h after drug administration. We assume that 2',2'-difluorodeoxyuridine, an active metabolite of gemcitabine, could be responsible for the toxic effect. We conclude that AF is an unusual, but potentially dangerous, side-effect of gemcitabine infusion. The arrhythmia should be suspected whenever patients complain of dyspnea and palpitations beginning 12-24 h after treatment. In these cases, the treatment of AF consists of anti-arrhythmic drugs in order to repristinate a sinus rhythm or control the heart rate.