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Métodos Terapéuticos y Terapias MTCI
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1.
Bull Cancer ; 97: 17-28, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20418201

RESUMEN

Advanced renal cell carcinoma is associated with a poor prognosis and is refractory to standard chemotherapy. Recent progress in the understanding of molecular biology and pathogenesis of renal cell cancer has been translated into the development of new therapeutic strategies. The management of metastatic RCC has been revolutionized with the development of targeted molecular therapies against VEGF-VEGFR and mTOR. Randomized phase III clinical trials demonstrated clinical benefit for patients with advanced RCC in overall survival and progression free survival. At the moment, six molecules have been approves in advanced RCC: cytokines (IL-2 and IFN), antiangiogenic therapies (sunitinib, sorafenib, bevacizumab) and mTOR inhibitors (Temsirolimus, everolimus). Nephrectomy is an important component of the multimodality treatment of mRCC. Prospective trials will be assessed the value of nephrectomy in patients treated by antiangiogenic therapies. Large randomized trial are ongoing to evaluate these new therapies in adjuvant setting.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Bencenosulfonatos/uso terapéutico , Bevacizumab , Carcinoma de Células Renales/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Everolimus , Humanos , Indoles/uso terapéutico , Interferones/uso terapéutico , Interleucina-2/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Renales/secundario , Neoplasias Renales/cirugía , Redes y Vías Metabólicas/efectos de los fármacos , Nefrectomía , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Sorafenib , Sunitinib , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/metabolismo
2.
Bull Cancer ; 97: 65-71, 2010.
Artículo en Francés | MEDLINE | ID: mdl-20418205

RESUMEN

The treatment of metastatic kidney cancer has dramatically changed in the last three years, with demonstration of efficacy of sunitinib, sorafenib, temsirolimus, bevacizumab combined with interferon and more recently everolimus. Although the international guidelines have recently been reviewed, some major questions are still open. Particularly, the best order of administration of these targeted therapies should be considered, since sequential schedule becomes usual with the availability of these new agents. At the same time, the tolerability and efficacy of the combination of the targeted therapies are under investigation in clinical trials. We report recent studies, mainly presented during the ASCO 2007 and 2008 congress. Furthermore, other studies are ongoing to answer other important questions, to optimize the treatment of this disease, such as the role of nephrectomy in case of synchronous metastatic disease, or the efficacy of the targeted therapies in different histological subtype than clear cell carcinoma, or in neoadjuvant and adjuvant settings.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencenosulfonatos/uso terapéutico , Bevacizumab , Terapia Combinada , Citocinas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Humanos , Indoles/uso terapéutico , Interferón-alfa/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/cirugía , Nefrectomía , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Sorafenib , Sunitinib , Serina-Treonina Quinasas TOR , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo
3.
Ann Oncol ; 21(5): 1027-31, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19850637

RESUMEN

BACKGROUND: This retrospective study evaluated the incidence of brain metastases in a subgroup of patients with metastatic renal cell carcinoma (RCC) who were randomly assigned to receive sorafenib, an oral multikinase inhibitor (400 mg b.i.d.), versus placebo in the phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET). PATIENTS AND METHODS: Patients enrolled in TARGET at two centres (Institut Gustave Roussy, Villejuif, France, n = 85; Central Clinical Hospital of Military Medical Academy, Warsaw, Poland, n = 54) made up the current subgroup, who were retrospectively evaluated for the incidence of brain metastases during follow-up. The association between treatment (sorafenib versus placebo) and occurrence of brain metastases was evaluated by univariate analysis. RESULTS: The overall incidence of brain metastases in patients receiving sorafenib was 3% (2 of 70 patients) compared with 12% (8 of 69 patients) in patients receiving placebo (P < 0.05). The incidence of brain metastases was also significantly lower in the sorafenib group after 1 (P = 0.0447) and 2 years (P = 0.005) of treatment compared with the placebo group. CONCLUSIONS: In this subpopulation, sorafenib may reduce the occurrence of brain metastases. Antiangiogenic therapy, such as sorafenib, could be an effective preventive therapy for brain metastases in advanced RCC.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Neoplasias Encefálicas/prevención & control , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Piridinas/uso terapéutico , Administración Oral , Anciano , Neoplasias Encefálicas/secundario , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Renales/patología , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Estudios Retrospectivos , Sorafenib , Tasa de Supervivencia
4.
Ann Oncol ; 19(7): 1308-1311, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18356135

RESUMEN

BACKGROUND: Chemotherapy has emerged as a standard treatment in patients with castration-refractory prostate cancer (CRPC). Consensus criteria are available to define response in CRPC as at least a 50% decline in serum prostate-specific antigen (PSA) confirmed 4 weeks later. The objective of this work was to study early serum PSA changes in patients under chemotherapy and to correlate these changes with subsequent response assessment. PATIENTS AND METHODS: Serum PSA levels were monitored every 3 weeks in 79 patients with CRPC treated with chemotherapy and a time course of serum PSA levels was obtained. Correlation with response was studied. RESULTS: According to consensus criteria, 21 (40%) and 20 (38%) patients achieved a PSA response and stabilization, respectively, after first-line chemotherapy. Among patients who achieved either a response or a stabilization, 8 of 41 (20%) had a serum PSA rise during the first 8 weeks of chemotherapy, followed by a subsequent decline in serum PSA. The same observation was made in patients receiving second-line chemotherapy: 6 of 20 patients achieving a response or stabilization had an initial serum PSA rise. The postchemotherapy increase in serum PSA could reach more than twice the baseline value. The duration of the PSA surge ranged from 1 to 8 weeks. When considering responders only, 6 of 30 (20%) had a postchemotherapy serum PSA surge, followed by a drop. CONCLUSION: Postchemotherapy PSA surges occur not infrequently in patients with CRPC who respond to chemotherapy. Physicians should be aware of this effect to avoid inadequate early discontinuation of chemotherapy.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/secundario , Orquiectomía , Antígeno Prostático Específico/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Docetaxel , Estramustina/administración & dosificación , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Cinética , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Prednisona/administración & dosificación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Sesquiterpenos/administración & dosificación , Síndrome , Taxoides/administración & dosificación , Resultado del Tratamiento
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