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BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.
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Asma , Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Rinitis/tratamiento farmacológico , Óxido Nítrico , Pólipos Nasales/tratamiento farmacológico , Calidad de Vida , Sinusitis/tratamiento farmacológico , Enfermedad CrónicaRESUMEN
Background: Dupilumab, an antiIL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. Objectives: We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. Methods: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. Results: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main CRSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. Conclusions: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP. (AU)
Antecedentes: El dupilumab, un anticuerpo monoclonal anti-IL-4 receptor alfa, ha sido aprobado recientemente para el tratamiento de la rinosinusitis crónica con pólipos nasales (CRSwNP) y asma de moderada a grave, demostrando un inicio rápido de los efectos clínicos. La CRSwNP se caracteriza por un infiltrado extenso inflamatorio de tipo 2 que puede evaluarse mediante el análisis de óxido nítrico exhalado extendido. Objetivos: En este estudio, investigamos si dupilumab se asocia con una mejora rápida en los parámetros de óxido nítrico extendido, la función pulmonar y los resultados clínicos en pacientes con CRSwNP. Métodos: Se incluyeron pacientes consecutivos con CRSwNP e indicación para ser tratados con dupilumab y fueron evaluados mediante el análisis de óxido nítrico extendido (exhalado, FENO; bronquial, JawNO y alveolar, componentes CalvNO; nasal, nNO) y función pulmonar, 15 y 30 días después del inicio del tratamiento; y en el caso de las variables clínicas (puntuación del tamaño de los pólipos nasales [NPS]; cuestionarios de calidad de vida; escalas analógicas visuales [EVA] para los principales síntomas principales, prueba de control del asma [ACT]) solo después de 30 días de iniciado el tratamiento. Resultados: Se incluyeron 33 pacientes. Todos los parámetros del análisis extendido del óxido nítrico y la función pulmonar mejoraron significativamente después de 15 días de tratamiento, permaneciendo estables a los 30 días de tratamiento. El NPS, las EVA para los principales síntomas de CRSwNP, el cuestionario de calidad de vida y el ACT mejoraron significativamente después de 30 días de inicio del tratamiento. Conclusiones: En pacientes con CRSwNP, el tratamiento con dupilumab se asocia con una mejoría muy rápida en la inflamación tipo 2 en todos los compartimentos de las vías respiratorias y esto se asocia con una mejor función pulmonar y los parámetros clínicos. (AU)
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Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Asma , Pólipos Nasales/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Encuestas y Cuestionarios , Enfermedad Crónica , Óxido Nítrico , Calidad de VidaRESUMEN
BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.
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INTRODUCTION: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. AREAS COVERED: We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma. EXPERT OPINION: We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.
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Asma , Biosimilares Farmacéuticos , Rinitis Alérgica , Asma/epidemiología , Asma/etiología , Asma/terapia , Desensibilización Inmunológica/efectos adversos , Humanos , Rinitis Alérgica/epidemiología , Rinitis Alérgica/terapiaAsunto(s)
Antiasmáticos/administración & dosificación , Asma/epidemiología , Cumplimiento de la Medicación/estadística & datos numéricos , Nebulizadores y Vaporizadores , Administración por Inhalación , Asma/diagnóstico , Asma/tratamiento farmacológico , Encuestas de Atención de la Salud , Humanos , Italia/epidemiologíaRESUMEN
No disponible
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Administración por Inhalación , Encuestas y Cuestionarios , Asma/tratamiento farmacológico , Escolaridad , ItaliaRESUMEN
Subjects with high hypnotizability scores (Highs) have been considered more prone to experience negative affect and more vulnerable to its autonomic effects with respect to low hypnotizable individuals (Lows). The aim of the study was to analyze the subjective experience, tonic skin conductance (SC), respiratory frequency (RF), heart rate (HR) and heart rate variability (HRV) of healthy Highs and Lows during a long-lasting, emotionally neutral task (Session R, 46 subjects) and a moderately threatening one (Session T, 35 subjects). At the end of the relaxing Session R, all participants reported an increased relaxation. At the end of the threatening Session T, only 20 subjects reported a decreased relaxation (effective T: eT subsample). Highs and Lows of this subsample reported a similarly reduced relaxation and showed a similarly increased skin conductance. HR and HRV did not differ between the two sessions and between Highs and Lows. Among the subjects not reporting decreased relaxation at the end of Session T (ineffective T: iT subsample, n=15), relaxation was deeper and associated with lower skin conductance in Highs, although HR and HRV did not differ between Highs and Lows. All together, the results do not support the hypothesis of higher proneness of Highs to experience negative affect and to exhibit the autonomic correlates of negative emotion.
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Emociones/fisiología , Frecuencia Cardíaca/fisiología , Hipnosis , Películas Cinematográficas , Estimulación Luminosa/métodos , Frecuencia Respiratoria/fisiología , Adulto , Sistema Nervioso Autónomo/fisiología , Femenino , Humanos , Hipnosis/métodos , Masculino , Relajación/fisiología , Relajación/psicología , Adulto JovenRESUMEN
Although the relationship between psyche and cancer dates back many centuries, and several studies were conducted on this topic during the last decades, the role of psychological factors in the development of cancer is still controversial. Although a lot of factors have been considered, attention has been focused mainly on stress, which has been evaluated also in experimental models. Generally, the results of case-control studies have been contradictory, and at times more stressfull events have been recorded in patients with benign tumors than in those with cancer. On the contrary, a higher incidence of stress-related cancers has not been documented in cohort studies. Since cancer is a genetic disease, it is difficult to hypothesize that psychological factors may permanently alter nucleotide sequence giving rise to multiple mutations needed for cancer development. At present, there is no sufficient evidence to affirm that psychological factors may contribute without doubt to cancer development.
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Depresión/complicaciones , Neoplasias/etiología , Neoplasias/psicología , Estrés Psicológico/complicaciones , Animales , Neoplasias de la Mama/etiología , Neoplasias de la Mama/psicología , Carcinoma/etiología , Carcinoma/psicología , Estudios de Casos y Controles , Estudios de Cohortes , Medicina Basada en la Evidencia , Humanos , Acontecimientos que Cambian la Vida , Trastornos de la Personalidad/complicaciones , Factores de Riesgo , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
The majority of breast cancers are actually diagnosed at an early stage. Selection of the best treatment in the adjuvant setting represents a paramount step to reduce the risk of recurrence and cancer-specific mortality. At the present time decision making is based on individualized risk assessment, that takes into account patient and tumor clinical-pathological characteristics. New available tools, such as gene expression profiling, offer the potential to provide accurate prognostic and predictive information, but they require further validation. The present article provides an overview of current strategies in adjuvant breast cancer setting, and addresses a number of unresolved questions related to the role of taxanes, trastuzumab and hormonal treatment.
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Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/química , Quimioterapia Adyuvante , Femenino , Humanos , Receptor ErbB-2/análisisRESUMEN
OBJECTIVE: To describe the oral health status and treatment needs of a sample of elderly people residing in nursing homes in Northern Italy. RESEARCH DESIGN: a sample of 595 elderly residents (mean age 83.2+/-9.2 yrs), with adequate cognitive skills were examined by six calibrated dentists. RESULTS: The sample (82% women) was divided into two groups: edentulous (43%) and dentate. In the edentulous group 58% wore dentures in both jaws, 8% in only one jaw and 34% had no dentures. The main problems were dirty or loose dentures and poor oral hygiene. In the dentate group the mean number of teeth was 8.4+/-7.4, 53% wore dentures (removable, fixed or a combination). Poor oral hygiene was found in 86%, root caries in 51% and coronal caries in 46%. Their main needs were professional cleaning (72%), oral hygiene instructions (62%) and tooth/root extractions (56%). While normative needs were noted for 82% of the whole sample, oral treatment needs were accurately perceived by only 20% of residents, poorly by 24%, while 46% indicated that they had no oral treatment needs.
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Caries Dental/epidemiología , Dentaduras/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Enfermedades de la Boca/epidemiología , Boca Edéntula/epidemiología , Casas de Salud , Anciano , Anciano de 80 o más Años , Estudios Transversales , Índice CPO , Reparación de la Dentadura , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Salud Bucal , Higiene Bucal , Autoevaluación (Psicología) , Extracción DentalRESUMEN
The treatment of refractory metastatic breast cancer is primarily palliative, without a significant impact on overall survival. Among the innovative combinations in this unfavourable setting, paclitaxel and gemcitabine showed a possible synergistic action and an encouraging activity in some clinical trials. This phase II study was carried out to evaluate paclitaxel-gemcitabine combination in very heavily pretreated advanced breast cancer on a bi-weekly schedule.Thirty-nine women with advanced breast cancer were treated with paclitaxel 150 mg/m2 as 3 hrs infusion, and gemcitabine 1,500 mg/m2 as 30 mins infusion, both drugs administered on days 1, 15, with cycles repeated every 28 days. All but two patients received granulocyte colony stimulating factor (G-CSF) on days 7 to 9 and 20 to 22 of every cycle. More than two third (71%) of the patients had previously received two or more chemotherapy regimens for advanced disease, including almost all active agents in this disease. Objective responses were observed in 18 out of 34 evaluable patients (53%; 95% CI, 36% to 70%). Disease remained stable in 7 patients (21%). Responses by sites were 67% in soft tissue and in bone, and 48% in visceral disease. Median time to progression and overall survival were 9 and 20 months, respectively. Treatment was well tolerated, with G3-4 neutropenia in 8%, and G 1-2 thrombocytopenia in 13% of the patients; non-hematological toxicities were mild, with G3 hepatotoxicity in 5% of the patients, and G3 peripheral neurotoxicity in 10% of the patients. Biweekly paclitaxel/gemcitabine combination with G-CSF support appears to be very active as salvage therapy in heavily pretreated breast cancer patients, with a very favourable safety profile.
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Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/administración & dosificación , Terapia Recuperativa/métodos , Adulto , Anciano , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.
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Neoplasias Colorrectales/radioterapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Radioisótopos de Itrio/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Humanos , Infusiones Intraarteriales , Microesferas , Estudios Prospectivos , Calidad de Vida , Dosificación Radioterapéutica , Factores de Tiempo , Resultado del Tratamiento , Radioisótopos de Itrio/efectos adversosRESUMEN
The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Levamisol/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy. PATIENTS AND METHODS: Patients entered in three consecutive trials of the GOIM (protocols no. 9706, 9901, and 2301) were reported in this analysis. A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen: Irinotecan 180 mg/m(2) on day 1 with LV5FU2 regimen (LV at 100 mg/m(2) administered as a 2-hour infusion before FU at 400 mg/m(2) as an intravenous bolus injection, and FU at 600 mg/m(2) as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2); the treatment was repeated every 2 weeks. RESULTS: 287 patients entered in these three trials, and 264 (92%) were evaluable for response. The overall response rate was 34.5% (95% confidence interval [CI]: 29% to 40%). When only assessable patients were analyzed, overall response rate was 37% (95% CI: 31% to 43%). Median time to progression, median duration of response and survival were 7 months, 10.5 months and 14 months, respectively. All but three patients were evaluable for toxicity which was globally mild; grade 3-4 toxicity was uncommon, and gastrointestinal disturbances were the most common. CONCLUSIONS: FOLFIRI regimen is effective and well-tolerated as first-line treatment in patients with advanced colorectal cancer. Further studies needed to evaluate the improvement in results with the addition of new drugs to this combination therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Carcinoma/secundario , Celecoxib , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Gástricas/patología , Taxoides/administración & dosificaciónRESUMEN
PURPOSE: The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial. PATIENTS AND METHODS: A total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of age > or = 70 and < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT-11 regimen, arm B 68 patients). Both treatments were repeated every two weeks. The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen. RESULTS: Thirty-three and sixty-four patients were evaluable in arm A and B, respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median duration of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 vs. 10 months, P = 0.0016). All patients were evaluable for toxicity which was mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms. CONCLUSIONS: The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literature, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: To assess the activity and toxicity of gemcitabine in locally advanced or metastatic soft tissue sarcoma patients (pts). PATIENTS AND METHODS: Gemcitabine was administered on days 1, 8, 15 every 4 weeks at a dose of 1.000/1.250 mg/m2, respectively, in pretreated or not pretreated pts. RESULTS: Eighteen pts entered this phase II trial; sixteen had been previously treated with anthracyclines and ifosfamide. A partial response was observed in a woman with fibrous malignant istocytoma, whereas in 7 pts the disease remained stable. Median time to progression was 4 months. The treatment was well tolerated. Grade 4 toxicity was not observed. CONCLUSIONS: These results do not suggest that gemcitabine, in the dose and schedule used in this trial, may be of value in the treatment of soft tissue sarcomas.
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Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Sarcoma/cirugía , Desoxicitidina/uso terapéutico , Femenino , Humanos , Estadificación de Neoplasias , Sarcoma/tratamiento farmacológico , Sarcoma/patología , GemcitabinaRESUMEN
PURPOSE: To evaluate the efficacy and toxicity of a sequential low-dose methotrexate (MTX) and 5-fluorouracil (5FU) regimen in the palliative treatment of patients with advanced colorectal cancer. PATIENTS AND METHODS: Enrolled in the study were patients with advanced colorectal cancer, refractory to 5FU + FA. Patients were treated with MTX 40 mg/m2 i.v. bolus d 1 and 8, 5FU 700 mg/m2 i.v. bolus d 2 and 9 (24 hours after MTX bolus). The cycle was repeated every 4 weeks. RESULTS: 48 patients entered the study, and 45 are evaluable. The overall response rate was 15% with 1 complete response and 6 partial responses. Eight patients obtained disease stabilization. Median time to progression was 9 months. Toxicity was mild. Grade 3 stomatitis was observed in 7 (15%) patients. CONCLUSIONS: Sequential MTX/5FU is a well tolerated regimen with mild antitumor activity in refractory advanced colorectal patients.
Asunto(s)
Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Metotrexato/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/toxicidad , Humanos , Leucovorina/toxicidad , Neoplasias Hepáticas/secundario , Metotrexato/toxicidad , Estadificación de Neoplasias , Estomatitis/inducido químicamenteRESUMEN
PURPOSE: To evaluate the activity and toxicity of docetaxel (TXT) as second line therapy in advanced soft-tissue sarcoma. PATIENTS AND METHODS: Adult patients (pts) with histologically proven locally advanced or metastatic soft tissue sarcoma, were treated with TXT at a dose of 100 mg/m2 in a 1-hour i.v. infusion every 21 days and steroid premedication with oral prednisone 50 mg twice a day for five days starting 24 hours prior to TXT. RESULTS: From November 1995 to May 1997, 19 pretreated pts entered the trial. Characteristics of the pts: males/females 11/8, median age 58 years (30-74), median WHO performance status 1 (0-2); histotypes: leiomyosarcoma 6 pts, malignant fibrous histiocytoma 6 pts, fibrosarcoma 2 pts, others 5 pts. No objective responses were seen. The disease remained stable in 8 pts (42%). Median time to progression was 3.5 months (range, 2-8), median survival 6 months (range, 2-20). The treatment was well-tolerated: the main side effect was hematological toxicity with G3/4 leukopenia and neutropenia in 58% of the pts; G3 anemia and thrombocytopenia occurred only in 1 case. Other toxicities were alopecia that was universal, G3 emesis in 1 pt, G3 diarrhea in 2 pts, G3 stomatitis in 1 pt. Mild fluid retention was recorded only in 2 pts. CONCLUSIONS: The results of this study do not suggest the use of TXT at this dosage and schedule in advanced soft tissue sarcoma.