Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
Ann Otol Rhinol Laryngol ; 127(7): 456-462, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29852745

RESUMO

OBJECTIVES: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated. METHODS: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted. Patients were treated with carboplatin (area under the curve: 5 mg/mL/min) on day 1, oral tegafur (250 mg/m2 twice daily) for 21 consecutive days, and cetuximab (400 mg/m2 as an initial 2-hour intravenous infusion, then 250 mg/m2 as a 1-hour weekly infusion for 3 weeks) for ≤6 cycles. Patients who responded to the therapy then received weekly cetuximab maintenance therapy. RESULTS: Treatment was well tolerated with a high level of compliance (relative dose intensity: 96%, 88%, and 81% for carboplatin, tegafur, and cetuximab, respectively). Grade 3-4 adverse events (AEs) were observed in 38% of patients (skin reactions in 17% of patients, anemia 4%, and neutropenia 3%). Grade 1-2 AEs included skin reactions (52% of patients), hypomagnesemia (20%), asthenia (19%), and anemia (13%). No venous thrombosis related to chemotherapy perfusion was observed. Over a median follow-up of 21 months, the median overall and progression-free survival were 11 and 6 months, respectively, and the overall response rate was 35%. CONCLUSIONS: Carboplatin plus oral tegafur and cetuximab is a safe, well-tolerated first-line therapy for recurrent or metastatic HNSCC.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imunossupressores/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Espanha/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida/tendências , Resultado do Tratamento
2.
Ther Adv Med Oncol ; 10: 1758835918764628, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623110

RESUMO

Immunotherapy through checkpoint inhibitors is now standard practice for a growing number of cancer types, supported by overall improvement of clinical outcomes and better tolerance. One anti-CTLA-4 antibody (ipilimumab), two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab and durvalumab) have been approved for clear benefits across diverse trials. Adverse events of an immune nature associated with these agents frequently affect the skin, colon, endocrine glands, lungs and liver. Most of these effects are mild and can be managed through transient immunosuppression with corticosteroids, but high-grade events often require hospitalization and specialized treatment. However, since immunotherapy is recent, physicians with clinical experience in the diagnosis and management of immune toxicities are frequently those who actively participated in trials, but many practicing oncologists are still not familiarized with the assessment of these events. This review focuses on the incidence, diagnostic assessment and recommended management of the most relevant immune-related adverse events.

3.
J Thorac Dis ; 9(Suppl 13): S1364-S1372, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29184675

RESUMO

Liquid biopsies have been heralded as a game changer in cancer management. Blood tests offer a minimally invasive, safe and sensitive complementary (or even alternative) approach for tissue biopsies. With lung cancer being the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide, due to the limitations of tissue sampling, liquid biopsies must urgently materialize in the clinic. In this short review, we will present the current applications of cell-free DNA (cfDNA) in lung cancer management, emphasizing on our own experience and previous work. We will also shortly comment on the challenges and need for a coordinated collaboration combining disciplines and sectors (from academia to health economies) in order to accelerate liquid biopsy development in lung cancer and other cancers.

4.
Ann Transl Med ; 5(19): 388, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29114546

RESUMO

The therapeutic possibilities for patients with metastatic melanoma have changed due to the development of targeted therapies that inhibit oncogenic signaling pathways as well as immune modulating therapies that unleash the patient antitumor immunity. These therapeutic changes have impressively increased the median overall survival of the patients. Considering the dramatic but transient responses that occur with targeted therapies for a subgroup of patients and the durable responses that can be achieved with immunotherapy in a subset of patients, a lot of effort is ongoing for the clinical development of combinations of these two therapeutic approaches. Herein we discuss the existing preclinical and clinical data for the combination of targeted therapies and immunotherapy focusing mainly on melanoma and non-small cell lung cancer (NSCLC).

5.
Expert Opin Investig Drugs ; 26(6): 713-722, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28463570

RESUMO

INTRODUCTION: Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development. Areas covered: This review will focus on new ALK inhibitors, currently in phase 1 or 2 clinical studies. We will also comment on the mechanisms of resistance to ALK inhibition and the strategies to delay or overcome resistance. Expert opinion: The therapeutic management of ALK-rearranged NSCLC has been greatly improved. Next-generation ALK inhibitors have shown differential potency against ALK rearrangements and ALK resistance mutations. The molecular profile of the tumor at the time of disease progression to crizotinib is crucial for the sequencing of novel ALK TKIs. Ongoing clinical studies will address key issues, including the optimal therapeutic algorithm and whether combinational approaches are more effective than single ALK inhibition for the outcome of ALK-rearranged NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Quinase do Linfoma Anaplásico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Progressão da Doença , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética
6.
Expert Opin Pharmacother ; 18(3): 295-304, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28103738

RESUMO

INTRODUCTION: Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach. Areas covered: In this review we are discussing the current treatment of relapsed or refractory lung cancer. We have thoroughly searched the literature (Pubmed) the last five years for studies or reviews published on the issue of second-line therapy in lung cancer using as key words, lung cancer, relapse, EGFR mutations, ALK rearrangements, chemotherapy and immunotherapy Expert opinion: The prognosis of lung cancer has been radically improved. Due to the recent development of checkpoint inhibitors, this also occurs for patients whose tumor's are not driven by a genetic alteration and who, until recently, derived only minimal benefit from chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma Anaplásico , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo
7.
BioDrugs ; 31(1): 63-73, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28000159

RESUMO

Targeting members of the human epidermal growth factor receptor family, especially EGFR and HER2, has been an established strategy for the treatment of tumors with abnormally activated receptors due to overexpression, mutation, ligand-dependent receptor dimerization and ligand-independent activation. Less attention has been paid to the oncogenic activity of HER3, although there is growing evidence that it mediates resistance to EGFR and HER2 pathway directed therapies. The main caveat for the development of effective HER3 targeted therapies is the absence of a strong enzymatic activity to target, as well as the limited potential for single-agent activity. In this review, we highlight the role of HER3 in cancer and, more specifically, in lung cancer. The basis for HER3 involvement in HER2 resistance and EGFR inhibition is discussed, as well as current pharmacologic strategies to combat HER3 inhibition.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Receptor ErbB-3/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Humanos , Neoplasias Pulmonares/metabolismo , Receptor ErbB-3/metabolismo
8.
J Thorac Dis ; 8(9): 2424-2426, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27746993
10.
World J Gastroenterol ; 20(42): 15820-9, 2014 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-25400468

RESUMO

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.


Assuntos
Adenocarcinoma/terapia , Antimetabólitos Antineoplásicos/administração & dosagem , Quimiorradioterapia , Fluoruracila/administração & dosagem , Laparoscopia , Terapia Neoadjuvante , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Endossonografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Espanha , Fatores de Tempo , Resultado do Tratamento , Procedimentos Desnecessários
11.
Eur Arch Otorhinolaryngol ; 271(2): 373-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23644939

RESUMO

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Cuidados Paliativos , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carboplatina , Cetuximab , Cisplatino , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Falha de Tratamento , Resultado do Tratamento
12.
Head Neck ; 35(2): E52-4, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22144378

RESUMO

BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland frequently develops lung metastases. In cases in which chemotherapy is indicated, resistance is a common phenomenon. New drugs, such as cetuximab, have been chosen to avoid this chemoresistance. METHODS AND RESULTS: A 54-year-old man was diagnosed with ACC of the right submandibular gland. He underwent a submandibular gland resection with adjuvant radiotherapy. Three years later, bilateral lung metastases were diagnosed and treated with various chemotherapy schedules, including paclitaxel without success. We obtained radiographic response, followed by disease stabilization for more than 1 year with the addition of cetuximab to paclitaxel administered at low weekly doses (metronomic schedule). CONCLUSION: This case demonstrates for the first time a reversion of primary resistance to chemotherapy in ACC that is currently considered chemoresistant by use of a combination of metronomic chemotherapy with new targeted agents such as cetuximab. Metronomic chemotherapy was also well tolerated and achieved long-term response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Adenoide Cístico/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias das Glândulas Salivares/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Biópsia por Agulha , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/cirurgia , Cetuximab , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Radioterapia Adjuvante , Medição de Risco , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA