RESUMO
The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed. We investigated the association between the RAS mutation status and clinical outcomes in terms of response rate, progression-free survival (PFS) and overall survival (OS). Mutations in RAS genes were observed in 47 (52.6%) patients (45 KRAS and 2 NRAS mutations). Patients with tumours harbouring RAS mutations were less suitable for primary tumour resection, were more likely to develop lung metastases, and received bevacizumab treatment for a shorter time period compared with those with wild-type tumours. The response rate to chemotherapy did not differ according to the RAS mutation status, and there were no significant differences in PFS [RAS mutation: 12 months, 95% confidence interval (CI): 8.7-15.2 vs. RAS wild-type: 12 months, 95% CI: 9.67-14.32; P=0.857] or OS (RAS mutation: 20 months, 95% CI: 14.3-25.6 vs. RAS wild-type: 24 months, 95% CI: 18.7-29.2; P=0.631). Patients with RAS mutation vs. those with RAS wild-type exhibited a favourable trend in PFS when treated with bevacizumab (13 months, 95% CI: 6.5-19.4 vs. 10 months, 95% CI: 4.2-15.7, respectively; P=0.07) and OS (27 months, 95% CI: 18.5-35.4 vs. 15 months, 95% CI: 12.4-17.5, respectively; P=0.22). In conclusion, RAS mutations are not a prognostic marker for PFS and OS in CRC patients receiving fluoropyrimidine-oxaliplatine treatment, with or without bevacizumab. RAS mutations are not predictive of the lack of efficacy of bevacizumab, and these patients appear to benefit from anti-angiogenic treatment.
RESUMO
Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy. Results from the recent Chaarted study, in patients that received docetaxel for the hormone sensitive disease, have contributed to change the initial treatment approach in metastatic prostate cancer, in order to adapt the best sequence for each patient. Those results have been supported by the Stampede trial. Stampede survival data showed not only a benefit in overall survival of adding docetaxel initially, but also a prolonged time to first skeletal related event. Now it is discussed in which setting the available drugs should be administered. This review article summarizes the treatment options for patients treated with docetaxel initially for hormone sensitive prostate cancer after developing progressive disease, and offers an algorithm proposal for treatment.
Assuntos
Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Imunoterapia , Masculino , Orquiectomia , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report.
RESUMO
The majority of deaths due to breast cancer occur in the context of complications secondary to metastatic disease. Trastuzumab, as a second line treatment, has shown a 15% objective response rate in patients with metastatic breast cancer. We present the case of a patient with two breast tumours, the second of more aggressive characteristics, with negative hormone receptors and c-erb-B2 +++, and with few therapeutic options due to her hepatic insufficiency secondary to metastatic disease; she was administered herceptin as monotherapy, and she had a complete clinical response. Trastuzumab has revolutionised the management of patients with metastatic breast cancer and Her-2- neu overexpression. Its combination with chemotherapy agents achieves a synergic activity.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Cisplatino/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Hepáticas/diagnóstico por imagem , Metástase Linfática , Mastectomia Radical Modificada , Metotrexato/uso terapêutico , Dosagem Radioterapêutica , Receptor ErbB-2 , Tamoxifeno/administração & dosagem , Tamoxifeno/uso terapêutico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Trastuzumab , Resultado do TratamentoRESUMO
Skin metastases as manifestation of internal neoplasias constitute a 0.8% of their initial presentation and generally imply an advanced stage of the disease and a short survival. The lung cancer metastasises to the skin in 2.8-24% of the cases, generally in advanced stages of the disease, although in 7-19%, skin metastases appear as first manifestation thereof. Sometimes, the study of the extent in the patients reveals that there are no metastases at other levels. We hereby present the case of a male diagnosed with a lung cancer whose first manifestation was the appearance of skin metastases.
Assuntos
Neoplasias Pulmonares/patologia , Neoplasias Cutâneas/secundário , Idoso , Humanos , Neoplasias Pulmonares/diagnóstico , MasculinoRESUMO
Small cell lung cancer is the most common cause of paraneoplastic Cushing's syndrome. The definitive treatment consists in surgical removal of the tumour, which is not possible in most of these cases (they are often diagnosed at advanced stages), and therefore it is frequently necessary adding the drug ketoconazol. We hereby present the case of a patient diagnosed with a metastatic carcinoma of unknown origin associated with two paraneoplastic syndromes: a Cushing's syndrome and a sensitive-motor axonal neuropathy, a very uncommon association.
Assuntos
Síndrome de ACTH Ectópico/etiologia , Adenocarcinoma/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Polineuropatia Paraneoplásica/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Antineoplásicos/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Anticorpos Anti-Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Testes de Função Hepática , Resultado do Tratamento , Ativação ViralAssuntos
Adenocarcinoma/secundário , Neoplasias da Medula Óssea/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Vértebras Cervicais/patologia , Neoplasias Pulmonares/patologia , Neoplasias da Coluna Vertebral/secundário , Vértebras Torácicas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Irradiação Craniana , Craniotomia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Lobo Frontal/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Taxoides/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patients general status deteriorated considerably and he was referred to the Oncology Service. There was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patients survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.