RESUMO
Hereditary Haemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome, is an autosomal dominant rare disease characterized by localized angiodysplasia. This is manifested as epistaxis, mucocutaneous and gastrointestinal telangiectases, and arteriovenous malformations in the pulmonary, cerebral or hepatic circulation. The prevalence is between 1 in 5,000 to 8,000, although it is higher in some regions. The most frequent clinical manifestation of HHT is epistaxis, normally from light to moderate from the 4(th) decade of life. However, many patients show severe epistaxis which may interfere with their quality of life. The epistaxis is due to telangiectasia on the nasal mucosa. These are focally dilated postcapilar venules, which in advanced phases show many layers of smooth muscle cells without elastic fibers, and very frequently directly connect with dilated arterioles. As a consequence of these vascular alterations, telangiectases are very sensitive to slight trauma and even to the friction with the air when breathing, which gives rise to nose bleeds. Unfortunately, there is no optimal pharmacological treatment for the epistaxis in HHT. The use of antifibrinolytic agents for the treatment of HHT has been studied recently by our group as an effective relief for nasal and gastric haemorrhages. This work represents a systematic review and the beginning of a systematic laboratory work we are now conducting in our lab to screen for "orphan drugs" as therapeutic agents in HHT. In this context, the use of hormones, immunosuppresants and anti-angiogenic agents are under preclinical study in our laboratory.
Assuntos
Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/terapia , Epistaxe/tratamento farmacológico , Epistaxe/etiologia , Epistaxe/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
BACKGROUND: Increased EGFR expression has been observed in many tumours. This overexpression usually correlates with a more advanced disease stage, a poorer prognosis and a worse chemotherapy response. EGFR inhibition has been considered an attractive approach in cancer treatment. Various strategies to intervene in EGFR signalling have been developed, mainly receptor inhibition of extracellular domain using anti-EGFR monoclonal antibodies and receptor inhibition on the intracytoplasmic domain using small-molecule tyrosine kinase inhibitors. Cetuximab and panitumumab are the most developed anti-EGFR monoclonal antibodies, and there is plenty of published information about their current status Objective/methods: In this review we focus on Zalutumumab, an IgG1 completely human anti-EGFR monoclonal antibody. RESULTS/CONCLUSIONS: Apart from EGFR inhibition, another anti-neoplastic effect of zalutumumab has also been postulated, mediated by immune mechanisms, specifically by antibody-dependent cell cytotoxicity. Zalutumumab is under clinical development, mainly for squamous cell cancer of head and neck and there are also ongoing trials in NSCLC and colorectal cancer.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/tendências , Descoberta de Drogas/tendências , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologiaRESUMO
The prognosis of advanced pancreatic adenocarcinoma is still poor nowadays. Gemcitabine in monotherapy (30-min infusion) has been the standard of treatment during the last decade, and many clinical trials have failed to demonstrate an improvement in overall survival (OS) with the addition of different drugs to gemcitabine, including cetuximab and bevacizumab. Nevertheless, some modest but interesting advances have been provided by combinations such as gemcitabine-erlotinib, gemcitabine-capecitabine and gemcitabine plus a platinum salt. In spite of this, survival results remain disappointing. Further research focused on new combinations, incorporating the new targeted therapies and identifying potential predictive factors of response are required to be able to offer effective tailored therapies to these patients.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Cetuximab , Ensaios Clínicos Fase III como Assunto , Desoxicitidina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Dose Máxima Tolerável , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Standard treatment of patients with T4b squamous cell head and neck cancer (T4b-SCHNC) is concomitant chemo-radiotherapy (CT-RT). Recent Phase III trials with Taxane containing induction chemotherapy (IC) suggest that IC could also play a role in this setting. The value of resecting the residual mass after IC and before RT is not yet clear in this context. METHODS: We present the results of a retrospective analysis. RESULTS: Between 1984 and 2001, 113 patients (patients) with T4b-SCHNC were treated at our institution with IC. Four patients dead during IC and 57 patients achieved a complete or a >90% partial response at primary and proceeded to definitive RT (or concomitant CT/RT). Surgical resection was reconsidered after IC and before RT in the other 52 patients. Surgery was performed in 13 of them: in 7 patients resection was R1, all of them had loco-regional progression (2 also developed systemic metastases) and median OS after surgery was 21 months, with no patient alive at 48 months. In the other 6 patients a R0 resection was performed: 3 of these patients had loco-regional relapses (1 also developed systemic metastases) and the other 3 patients remain alive and disease free 56, 62 and 72 months after surgery. Considering the 52 patients that achieved less than a 90% partial response at primary with IC, overall survival was equivalent when no Resection or an R1 resection was performed after IC (5 year OS 8 vs. 0%, lrk, p=0.74), but a statistically significant improvement in OS was observed when an R0 resection was obtained (5 years OS 50%, lrk, p=0.02). CONCLUSIONS: R0 resections after IC and before RT could indicate an improvement in OS in patients with T4b-SCHNC that obtain less than a 90% PR at primary after IC. We consider that this approach deserves further research in prospective clinical trials.