RESUMO
Sir Williams Osler, the father of Modern Medicine, recognized more than one century ago, that "If it were not for the great variability among individuals, medicine might as well be a science and not an art". Nevertheless today, in our opinion this paradigm is presently in crisis. Clinical medicine starts to be a science thanks to this variability that is generating a personalized medicine based on the concepts of pharmacogenetic and pharmacogenomic. In the Medical Oncology field this era has begun: today the determination of mutations in several given genes such as Her2, KRAS, EGFR, ALK, and BRAF is translating into a individualized strategy that produces benefits that are clearly superior to present indiscriminate therapeutic decisions. This strategy is more active, more safe and also more efficient.
Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/genética , Medicina de Precisão , Biomarcadores , Genes Neoplásicos , HumanosRESUMO
It is estimated than one out of 3 people in Spain will suffer of cancer along the life. In fact cancer is responsible for the 25% of deaths in our country. The good news is that the overall survival at five years is around 66%. For the future it will be necessary to review the way we are developing clinical trials in order to approve the drugs by the regulatory agencies. Other important topics is how to approach the long survivor and also the economic issues related to it. In addition it will be also critical to establish the adequate policy for the prevention of cancer (primary and secondary) including the early diagnosis, the screening and the genetic counsel.
Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Humanos , Sobrevida , Resultado do TratamentoRESUMO
The natural history of metastasic colorectal cancer has being clearly modified in terms of response rate, time to progression and overall survival, once the antiEGFR monoclonal antibodies (cetuximab and panitumumab) have emerged in combination with the standard cytotoxic chemotherapy (FOLFOX and FOLFIRI). However, the benefit from cetuximab and panitumumab is only confined to KRAS-wild type (KRAS-wt) colorectal tumors, while KRAS-mutated tumors do not respond to these drugs. The 65% of colorectal tumors are KRAS-wt tumors, but efficacy of antiEGFR therapies is detected only in 60-70% of these KRAS-wt tumors. Other biomarkers and molecular pathways must be involved in the response of the antiEGFR therapies for the KRAS-wt colorectal tumors, such as the EGFR ligands, the EGFR-phosphorilated levels, the number of EGFR copies, the status of the KRAS effecter B-RAF and the alternative intracellular signaling pathways PIK3CA/PTEN/AKT and JAK/STAT. A battery of these biomarkers is needed to select the most sensitive patients to the antiEGFR therapies. This pattern may represent a novel favorable cost-effectiveness tool to develop tailored treatments. A review of these biomarkers and molecular pathways, involved in the antiEGFR therapies response, is performed.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Receptores ErbB/antagonistas & inibidores , Anticorpos Monoclonais Humanizados , Biomarcadores , Cetuximab , Neoplasias Colorretais/genética , Genes ras , Humanos , Metástase Neoplásica , PanitumumabeRESUMO
BACKGROUND: In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA. PATIENTS AND METHODS: In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum- and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse- free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed. RESULTS: From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54-72; range 45-78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0-1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m2 (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1-46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8-14.9) and median OS had not been reached at the time of analysis. Patients with PS< or =1 at diagnosis had a higher RFS [p=0.051 (CI 95% 0.90-0.96)]. Toxicity was generally mild and haematologic events were the most frequent. Non-haematologic toxic effects of chemotherapy were asthenia/ anorexia (12.2%), nausea/vomiting (12.2%) and peripheral neuropathy (17%), but severe toxic effects (grade 3 or greater) were uncommon (<10%). We did not observe treatment-related deaths. CONCLUSIONS: Platinum-taxane-based adjuvant chemotherapy in IB-IIIA NSCLC following complete resection is feasible, well tolerated and can be delivered in most patients in the adjuvant setting. Ongoing molecular studies may have value in determining which patients will benefit from adjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
The principal objective of the translational research in Oncology is to translate the knowledge derived from the basic research to the clinical practice as soon as possible. The goal is to develop and maximize the concepts of oncopharmacogenomic and oncopharmacogenetic. In tis context it will be absolutely necessary that hospitals integrate the basic and clinical research in translational research units with the appropriate resources.
Assuntos
Oncologia/tendências , Neoplasias/terapia , Pesquisa Biomédica , Biotecnologia , Institutos de Câncer , Feminino , Previsões , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/genética , Farmacogenética , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , EspanhaRESUMO
AIM: Studies in some countries suggest that cancer pain is often not adequately controlled, but little is known about the situation in Spain. The objective of this study was to identify medical oncologists' perceptions about pain management in their patients. METHODS: Two-round Delphi survey of 24 medical oncologists from 22 large, geographically diverse hospitals in Spain. Physicians rated each of 150 statements on a Likert scale (1=strongly disagree; 5=strongly agree). The mean, standard deviation and frequency of replies in three agreement categories were calculated for each item. Statements allowing comparison of oncologists' perceptions of how pain is managed in routine clinical practice with how it should be managed were grouped together and analyzed. RESULTS: The most notable discrepancies between the real and the ideal occurred in the failure to provide written information or to confirm that patients understand what they are told, the lack of comprehensive and systematic evaluation of pain, and the lack of use of non-pharmacological treatments (NPTs) for cancer pain. CONCLUSIONS: Medical oncologists need to improve their communication skills, providing patients with both written and verbal information about their disease and the plan for pain management. Pain should be evaluated at each patient visit using validated scales, and greater attention should be paid to the possible use of NPTs.
Assuntos
Atitude do Pessoal de Saúde , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Neoplasias/complicações , Dor Intratável/terapia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Analgésicos/normas , Analgésicos/uso terapêutico , Protocolos Clínicos/normas , Humanos , Pessoa de Meia-Idade , Dor Intratável/etiologia , Educação de Pacientes como Assunto/normas , Educação de Pacientes como Assunto/estatística & dados numéricos , Relações Médico-Paciente , EspanhaRESUMO
Malignant melanoma is the most rapidly increasing cancer in the world. Metastatic disease occurs in 20% of patients, and prognosis in these cases is poor. We report the case of a woman who presented breast metastasis as the first sign of recurrence of a melanoma.
Assuntos
Neoplasias da Mama/secundário , Melanoma/secundário , Neoplasias Cutâneas/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Calcinose/diagnóstico por imagem , Terapia Combinada , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Mamografia , Mastectomia , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Pessoa de Meia-Idade , Proteínas Recombinantes , Neoplasias Cutâneas/cirurgia , UltrassonografiaRESUMO
Current issues of adjuvant therapy for colon cancer concern the introduction of drugs other than fluorouracil-5/leucovorin (5-FU/LV), the benefits for stage II patients, the use of new primary endpoints and the influence of age on treatment benefits. These issues were addressed in a panel discussion and the conclusions were the following: FOLFOX4 is the first regimen that shows superiority over 5-FU/LV. The use of 3-year disease-free survival as primary endpoint could encourage the quicker adoption of improved therapeutic strategies into clinical practice. Available data suggest that there are some benefits for stage II patients, and the decision needs to be individualised for each patient. Further, therapeutic decisions based solely on the patient's age are inappropriate, and geriatric assessment tools will help in making this decision. This information would improve patient and physician understanding of the recent data regarding the potential benefits of adjuvant therapy.
Assuntos
Neoplasias do Colo/terapia , Fatores Etários , Idoso , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , HumanosRESUMO
INTRODUCTION: Cetuximab is a chimeric monoclonal antibody targeting the EGFR, which has proven effective in patients with metastatic colorectal cancer (mCRC), wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS). AREAS COVERED: The aim of this manuscript is to discuss the current impact of cetuximab in the most important scenarios of mCRC. We review the currently available data regarding the role of other biomarkers, such as the mutational status of neuroblastoma RAS viral (v-ras) oncogene homolog in identifying patients who could benefit most from anti-EGFR. In addition, a review is included of the most relevant clinical trials that have assessed the effectiveness of cetuximab in the management of patients with potentially resectable metastatic disease and in the first-line treatment of wild-type KRAS mCRC, as well as the impact of this anti-EGFR agent on patient quality of life. EXPERT OPINION: Cetuximab has had a progressive clinical development from the earliest to the later stages of the evolution of mCRC and has been consolidated as a therapeutic option for all scenarios of unresectable disease. Patient selection by analysis of KRAS mutations has been a fundamental event to increase efficiency, being a dynamic process that continues in assessment. There are few comparative data with other biological agents in combination with chemotherapy, although data from a recent study are promising.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab , Neoplasias Colorretais/genética , Genes ras/genética , Humanos , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Resultado do Tratamento , Proteínas ras/genéticaRESUMO
PURPOSE: VIA scale is a dynamic performance status tool of the peripheral venous system that is divided into five different grades, composed of three parameters: number of observable puncture points; optimal catheter size for cannulation and ease of performing venipuncture and risk of extravasation. METHODS: Prospective single-center, observational, open, non-randomized study divided into two phases. In the first longitudinal phase, we studied the clinical characteristics and the changes in their peripheral venous systems during intravenous chemotherapy for 16 patients (n=16) for an average period of 24 months. In the second transverse phase, we measured the vein's diameter at the selected puncture points with a high-resolution ultrasound and paired this figure with VIA scale. We selected a group of oncology patients (n=52) and a control group (n=56). RESULTS: In the first phase, the level of agreement between the three reviewers was excellent. The second step was to assess the relationship between the measurements obtained with ultrasound and the VIA scale. The vein diameter measurements show a decrease directly related to the assessment of observers in the VIA scale. CONCLUSIONS: The VIA scale is a simple, easy and practical method for classification of the peripheral venous system in terms of vascular access. The practical application of our VIA scale significantly increases the quality of life of patients by increasing the chances of successful venipuncture and cannulation and thus reducing the risk of extravasation and material costs, allowing both an economical and a safe venous assessment tool.
Assuntos
Antineoplásicos/administração & dosagem , Cateterismo Periférico , Técnicas de Apoio para a Decisão , Flebotomia , Veias/diagnóstico por imagem , Adulto , Idoso , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Esquema de Medicação , Desenho de Equipamento , Feminino , Humanos , Infusões Intravenosas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Flebotomia/efeitos adversos , Flebotomia/instrumentação , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Espanha , Fatores de Tempo , Ultrassonografia , Dispositivos de Acesso Vascular , Adulto JovemRESUMO
Therapy for metastatic colorectal cancer has been improved in terms of response rate, time to progression and overall survival by the emergence of anti-EGFR monoclonal antibodies (cetuximab and panitumumab) in combination with standard cytotoxic chemotherapy (oxaliplatin or CPT-11-based combinations). However, the benefits of cetuximab and panitumumab are confined to KRAS wild-type (KRAS-wt) colorectal tumours; KRAS-mutated tumours rarely respond to these drugs. Of all colorectal tumours, 65% are KRAS-wt tumours, but anti-EGFR therapies are effective for only 60-70% of these. Therefore, other biomarkers and molecular pathways must be involved in the response to anti-EGFR therapies in KRASwt colorectal tumours. Factors that may explain the lack of response include EGFR ligands, EGFR phosphorylation levels, the number of EGFR copies, the status of the KRAS effector B-RAF and the alternative intracellular PIK3CA/ PTEN/AKT and JAK/STAT signalling pathways. A battery of biomarkers is needed to select the patients that will be most sensitive to anti-EGFR therapies. Such patterns may be a novel and cost-effective tool to develop tailored treatments. This manuscript will review biomarkers and molecular pathways that are involved in the tumour response to anti-EGFR therapies.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Biomarcadores/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Proteínas ras/metabolismo , Anticorpos Monoclonais/química , Anticorpos Monoclonais Humanizados , Proliferação de Células , Cetuximab , Ensaios Clínicos como Assunto , Genes ras , Humanos , Ligantes , Modelos Biológicos , Metástase Neoplásica , Panitumumabe , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de SinaisRESUMO
Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in nonresponders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended.
Assuntos
Anemia/complicações , Anemia/tratamento farmacológico , Hematínicos/uso terapêutico , Oncologia/métodos , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Transfusão de Sangue , Doença Crônica/terapia , Ensaios Clínicos como Assunto , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Humanos , Ferro/metabolismo , Guias de Prática Clínica como Assunto , EspanhaRESUMO
Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens.
Assuntos
Fatores Estimuladores de Colônias/uso terapêutico , Neoplasias/complicações , Neutropenia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Consenso , Quimioterapia Combinada , Humanos , Oncologia , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Neutropenia/urina , EspanhaRESUMO
The tolerability of chemotherapy has been significantly improved by the advent of effective drugs and protocols for the amelioration of chemotherapy-induced nausea and vomiting. Variables such as the timing of nausea and vomiting (acute, delayed or anticipatory) and the emetogenicity of the chemotherapy must be taken into account in developing guidelines for antiemetic prophylaxis and treatment. Although there are a number of 5-hydroxytryptamine antagonists available, the clinical differences between them are small. The use of drugs with a different mechanism of action, such as the recently introduced neurokinin-1 receptor antagonist aprepitant, may be a useful adjunct to 5-hydroxytryptamine-3 receptor antagonists or steroid prophylaxis. The addition of aprepitant to standard antiemetic regimens increases the proportion of complete responses to antiemetic therapy. For the use of highly emetogenic chemotherapy in oncology a combination of 5-hydroxytryptamine-3 receptor antagonist, dexamethasone and aprepitant is recommended in the acute phase, and dexamethasone plus aprepitant during the subsequent days (many patients do not have their symptoms controlled by 5-hydroxytryptamine-3 receptor antagonist and steroid alone). In either case, lorazepam can be added as required. For moderately emetogenic chemotherapy, a regimen of 5-hydroxytryptamine, dexamethasone and aprepitant is recommended in the acute phase, followed by aprepitant alone in the delayed phase. Alternatively, a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone can be used in the acute phase, followed by dexamethasone for prophylaxis in the delayed phase. For chemotherapy with a low emetogenicity, either dexamethasone, metoclopramide, prochlorperazine or triethyperazine alone is recommended. No prophylaxis is generally required during the delayed phase and indeed may not be necessary during the acute phase either.