Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Riesgo , Vidarabina/uso terapéuticoRESUMEN
PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos/administración & dosificación , Ascitis/tratamiento farmacológico , Bevacizumab/administración & dosificación , Neoplasias Gastrointestinales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/etiología , Método Doble Ciego , Femenino , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/patología , Humanos , Inyecciones Intraperitoneales , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m(2)/day 1 plus capecitabine 1000 mg/m(2) bid/days 1-14 or with irinotecan 200 mg/m(2)/day 1 plus capecitabine 800 mg/m(2) bid/days 1-14 both every 21 days. The primary end point was 6 months progression-free survival (PFS). RESULTS: A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx-bevacizumab: n = 127; mCapIri-bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%-84%) and 84% (95% CI, 77%-90%). Median PFS and OS were 10.4 months (95% CI, 9.0-12.0) and 24.4 months (95% CI, 19.3-30.7) with CapOx-bevacizumab, and 12.1 months (95% CI, 10.8-13.2) and 25.5 months (95% CI, 21.0-31.0) with mCapIri-bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab. CONCLUSIONS: Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Diarrea/inducido químicamente , Diarrea/diagnóstico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Resultado del TratamientoRESUMEN
BACKGROUND: An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory. METHODS: Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate. RESULTS: A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis). CONCLUSIONS: This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Capecitabina , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina , GemcitabinaRESUMEN
BACKGROUND: Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles. RESULTS: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months. CONCLUSION: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/secundario , Terapia Recuperativa , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/efectos adversos , Bortezomib , Capecitabina , Carcinoma/tratamiento farmacológico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Enfermedades Hematológicas/inducido químicamente , Humanos , Dosis Máxima Tolerada , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Análisis de Supervivencia , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Levels of experience and competence in palliative medicine vary considerably among physicians. The aim of the study was to collect information from specially interested general practitioners on education, pivotal lectures and experience regarding the delivery of palliative care. SUBJECT AND METHODS: 92 general practitioners (41 women and 22 men) attending a basic course in palliative medicine were asked to fill in a standardized questionnaire relating to their knowledge and experience of palliative medicine. 63 responded (68%), 54 in general private practice, nine worked in a hospital. The same number worked in urban and in rural health care facilities. RESULTS: The majority of those questioned (53%) gained their first experience in palliative medicine as junior hospital doctors about a quarter (26%) only after starting in private practice. Many of the doctors (31%) admitted to taking more interest in palliative medicine only after having made mistakes, a significant percentage (20%) after the death of a relative. 28% expressed the view that practical courses were an important part in learning about palliative medicine. CONCLUSIONS: The implementation of practice-based c tuition of medical students and of continuing education of established general practitioners and hospital physicians in palliative medicine is indispensable.
Asunto(s)
Competencia Clínica , Educación Médica Continua/organización & administración , Conocimientos, Actitudes y Práctica en Salud , Cuidados Paliativos/normas , Médicos de Familia/educación , Médicos de Familia/psicología , Femenino , Alemania , Humanos , Masculino , Cuidados Paliativos/psicología , Relaciones Médico-PacienteRESUMEN
Internal and external fixation devices are widely used in traumatology and orthopedic surgery. Early radiographic detection of complications due to bone surgery is based on a thorough knowledge of the different types of implants and their biomechanical properties. The development of early and late complications is demonstrated.
Asunto(s)
Fijación Interna de Fracturas/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Falla de Equipo , Migración de Cuerpo Extraño/diagnóstico por imagen , Humanos , Osteonecrosis/diagnóstico por imagen , Seudoartrosis/diagnóstico por imagen , RadiografíaRESUMEN
Oscillation of cyclic AMP and in the activity ratio of cyclic AMP-dependent protein kinase and of glycogen phosphorylase with the cardiac cycle were demonstrated in the canine heart in situ. For tissue sampling an ECG (R-wave)-triggered, automatically working push-freeze-drill apparatus was developed which allows intraventricular cryobiopsies from the left ventricular muscle of anaesthetized open-chest dogs. The nucleotide cyclic AMP oscillated with the cardiac cycle during normal working condition, the higher cyclic AMP level occuring during systole. Cyclic GMP was assayed to be without oscillatory changes during the contraction-relaxation cycle. The rise in the activity ratio of protein kinase was found to coincide with the maximum in the level of cyclic AMP. Propranolol pretreatment prevents the transient in the level of the nucleotide as well as in the activity ratio of the kinase indicating i) a causal relationship between these changes and ii) a neurohumoral, beat-to-beat regulation by catecholamines released from the sympathetic nerve endings within the heart. Contrary the activity ratio of phosphorylase retains its transient changes during the cardiac cycle in the presence of propranolol, indicating a Ca-mediated activation of phosphorlase kinase during the contraction process.
Asunto(s)
1-Propanol/farmacología , AMP Cíclico/metabolismo , Miocardio/metabolismo , Fosforilasas/metabolismo , Proteínas Quinasas/metabolismo , Animales , Calcio/metabolismo , GMP Cíclico/metabolismo , Diástole/efectos de los fármacos , Perros , Electrocardiografía , Activación Enzimática/efectos de los fármacos , Femenino , Masculino , Contracción Miocárdica , Miocardio/enzimología , Sístole/efectos de los fármacosRESUMEN
The activity ratio of cyclic AMP-dependent protein kinase and glycogen phosphorylase were determined at various stages of the contraction cycle in the canine heart in situ. Both activity ratios vary transiently throughout the contraction-relaxation cycle, the higher values occurring during systole. The rise in the activity ratio of protein kinase was found to coincide with the maximum in the level of cyclic AMP. Propranolol pretreatment prevents the transient in the level of the nucleotide as well as in the activity ratio of the kinase indicating i) a causal relationship between these changes and ii) a neurohumoral, beat-to-beat regulation by catecholamines. Contrary the activity ratio of phosphorylase retains, in the presence of propranolol, its transient changes during the cardiac cycle, probably caused by a Ca2+-mediated activation of phosphorylase kinase during the contraction process.
Asunto(s)
Contracción Miocárdica , Miocardio/metabolismo , Fosforilasas/metabolismo , Proteínas Quinasas/metabolismo , Animales , AMP Cíclico/metabolismo , Perros , Activación Enzimática/efectos de los fármacos , Femenino , Masculino , Propranolol/farmacología , Receptores Adrenérgicos beta/metabolismoRESUMEN
Oscillations of cyclic AMP with the cardiac cycle were demonstrated in the canine heart in situ. For tissue sampling an ECG(R-wave)-triggered, automatically working push-freeze-drill apparatus was employed which allowed intraventricular cryobiopsies from the left ventricular muscle of anaesthetized open-chest dogs. The nucleotide cyclic AMP oscillated with the cardiac cycle during normal working conditions, the higher cyclic AMP values occurring during systole. Cyclic GMP was assayed to be without oscillatory changes during the contraction-relaxation cycle of the heart.