Renato Sotto-Mayor

An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

AIM Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC) versus docetaxel, pemetrexed and best supportive care. MATERIALS AND METHODS Cost-minimisation and cost-utility analysis were performed. Time horizon of two years. Portuguese National Health System (NHS) perspective was applied. Survival and time to progression were obtained from three clinical trials. Base-case analysis: 2nd or 3rd line patients with advanced or metastatic NSCLC. Quality Adjusted Life Years (QALYs) were obtained from a UK study. Resource consumption was estimated by a Portuguese panel of experts. Costs were calculated according to official Portuguese databases (updated to 2008). Only direct health costs were applied. Annual discount rate: 5%. Sensitivity analysis included different subpopulations, a three year time horizon and a probabilistic analysis. RESULTS The cost per patient was lower with erlotinib (26,478 euro) than docetaxel (29,262 euro) or pemetrexed (32,762 euro) and higher than best supportive care (16,112 euro). QALYs per patient were higher with erlotinib (0.250) than docetaxel (0.225), pemetrexed (0.241) or best supportive care (0.186). Erlotinib was dominant in the cost-utility analysis, with a lower cost and a higher efficacy than docetaxel and pemetrexed. The sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS The use of erlotinib instead of docetaxel or pemetrexed could contribute to annual savings for the NHS (substitution rates: 5%-65%) ranging from 135,046 euro-1,755,602 euro (docetaxel replacement) and 291,801 euro-3,793,409 euro (pemetrexed replacement), with a gain in terms of QALYs.

Avaliação económica do erlotinib, docetaxel, pemetrexedo e tratamento de suporte no tratamento de segunda ou terceira linhas de doentes com cancro do pulmão de não pequenas células

Resumo Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmao de nao pequenas celulas (CPNPC) avancado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte. Material e metodos: Analises de minimizacao de custos e custo-utilidade. Horizonte temporal: dois anos. Perspectiva do Sistema Nacional de Saude (SNS) portugues. Sobrevivencia e tempo ate progressao obtidos a partir de tres ensaios clinicos. Analise-base inclui doentes com CPNPC avancado ou metastizado em segunda ou terceira linhas. Anos de vida ajustados pela qualidade (ou QALY) obtidos a partir de estudo no Reino Unido. Consumo de recursos estimado por painel de peritos portugueses. Incluiram-se apenas custos directos, obtidos a partir de fontes oficiais (precos actualizados para 2008). Taxa de actualizacao anual: 5%. Analises de sensibilidade: diferentes subpopulacoes, horizonte temporal a tres anos e analise probabilistica. Resultados: O custo total/doente foi menor com erlotinib (26 478€) versus docetaxel (29 262€) ou pemetrexedo (32 762€) e superior versus tratamento de suporte (16 112€). Obtiveram-se QALY/doente mais elevados com erlotinib (0,250) versus docetaxel (0,225), pemetrexedo (0,241) ou tratamento de suporte (0,186). Assim, o erlotinib mostrou-se “dominante” em segunda ou terceira linhas versus docetaxel e pemetrexedo. A analise de sensibilidade comprova a robustez dos resultados. Conclusoes: A substituicao de docetaxel ou pemetrexedo por erlotinib poderia contribuir para uma reducao anual dos gastos do SNS que se estima (taxas substituicao: 5%-65%) com uma variacao entre 135 046€-1 755 602€ e entre 291 801€-3 793 409€, respectivamente, e com ganho em termos de QALY. Rev Port Pneumol 2008; XIV (6): 803-827

Four years’ follow up at a smoking cessation clinic

UNLABELLED Smoking is an important cause of pulmonary pathology and this addiction can be regarded as a chronic, recurrent disease. The benefits of smoking cessation are unquestionable and all physicians should become more active and assertive in recommending it. AIM To characterise the population seeking medical support for smoking cessation and understand why some successfully stop smoking and others do not. MATERIAL AND METHODS Retrospective analysis of medical records of outpatients in follow-up between January 2003 and June 2006. Age, gender, age at smoking initiation, smoking burden (number of pack-years), associated diseases, degree of dependence (Fagerström test for nicotine addiction), prior attempts at and motivation for smoking cessation, need for cognitive/behavioural support and success and abandonment rates were evaluated. RESULTS Five hundred and twenty six patients were studied, 50% male with an average age of 45.5+/-11.4 years. Almost half (43.1 %; n=227) of the patients started smoking before the age of 15. Average smoking burden was 35.8+/-20 pack-years although 21.4% (n=113) smoked more than 50 pack-years. Respiratory disease was present in 52.1% (COPD, 39.9% and others, 12.2%) and cardiovascular disease in 14.6% of the patients. In 46% of patients (n=242) a relevant psychiatric disorder was identified; depression (21.4%), anxiety disorder (19.4%), other dependencies (2.1%) bipolar disorder (1.5%) and schizophrenia (0.6%). The evaluation of degree of addiction revealed maximum level in 69.7% of the patients (n=380). Many patients (72.2%; n=380) reported prior attempts to quit smoking. The strongest reasons for giving up smoking were concern over health (83.5%), financial issues (8.2%) and search for better quality of life (5.7%). Most patients (81.7%; n=430) had undergone nicotine replacement therapy; skin patches (53.3%), chewing gum (1.1%) or both (45.6%). Psychopharmacological treatment included administration of sedative-hypnotics (86.5%), bupropion hydrochloride (2.3%) and antidepressants (0.6%). Seventy six patients (14%) benefited from cognitive/ behavioural support. Two hundred and twenty three patients (42.4%) were successful in giving up smoking while 219 (41.6%) abandoned follow up, the majority after the first appointment. Most patients that abandoned follow up reported lack of motivation and the price of therapy. CONCLUSIONS The population under study had a high rate of psychiatric disorders and a high level of dependence and lack of motivation that might justify the drop-out rate. Successful treatment was associated with close follow up, behavioural support and pharmacological therapy.

Terapêutica do carcinoma pulmonar não de pequenas celulas

RESUMO No presente artigo de revisao o autor aborda a terapeutica do carcinoma pulmonar nao de pcquenas celulas em funcao do estadio de apresentacao da doenca, dando especial relevo a sua abordagem multidisciplinar, no sentido de ultrapassarmos o mau prognostico que o seu diagnostico ainda acarreta. Discute o Iugar das diferentes modalidades terapeuticas, a terapeutica da recidiva e da progressao tumorais, a do cancro do pulmao no doente idoso, o papel dos novos farmacos e as potencialidades dos novos alvos terapeuticos a nivel da biologia celular e molecular. REV PORT PNEUMOL 2002; Vlll (3): 237-259

Lavagem pulmonar total – A propósito de quatro casos de proteinose alveolar

Resumo A lavagem pulmonar e uma tecnica desenvolvida na decada de 60 do seculo xx com o intuito de remocao fisica de material proteinaceo dos bronquios, em doentes com proteinose alveolar, levando a uma melhoria clinica e funcional. A tecnica foi evoluindo e o que era inicialmente realizado com anestesia local a um segmento do pulmao e actualmente realizado sob anestesia geral, sequencialmente, a ambos os pulmoes. A presente revisao descreve a tecnica de lavagem pulmonar total, a sua principal indicacao, a proteinose alveolar e, a proposito, relatamos alguns dados relativos a experiencia do nosso servico, onde a realizam com regularidade desde 2002.

Tabaco e genética

O tabagismo constitui uma das maiores ameaças à saúde humana nos nossos dias. Cerca de 1,1 bilião de indivíduos do mundo inteiro são fumadores e as doenças relacionadas com o fumo do tabaco49 são responsáveis por uma morte em cada 10, isto é, 3 milhões de mortes por ano42. Calcula-se que metade dos fumadores morra por efeitos do tabagismo e 1/3 destes antes dos 65 anos62. Se até recentemente a epidemia do tabaco tinha um impacto predominante nos países desenvolvidos, actualmente ela está a alastrar-se, dramaticamente, aos menos desenvolvidos, estimando-se que, em 2030, as patologias relacionadas com o fumo do tabaco sejam a principal causa de morte em todo o mundo29. Dado que o tabagismo é um factor de risco modificável e evitável, o tratamento e prevenção desse hábito nefasto representa uma oportunidade para a promoção da Saúde Pública. Apesar das múltiplas campanhas antitabágicas implementadas a partir de 1975 nos países desenvolvidos, que aí levaram a uma diminuição do número de fumadores, nos países em desenvolvimento assistiu-se a um aumento de cerca de 50%45. A Organização Mundial de Saúde estima que, em todo o mundo, 47% dos homens e 12% das mulheres com idade igual ou superior a 15 anos sejam fumadores11. Cerca de 25% dos adultos dos Estados Unidos da América continua a fumar, apesar de grande Chefe de Serviço de Pneumologia do Hospital de Santa Maria, Lisboa. Assistente Convidado da Faculdade de Medicina de Lisboa. RENATO SOTTO-MAYOR TEXTOS

Linfoma intravascular do pulmão: A propósito de um caso clínico com boa resposta à terapêutica

Intravascular lymphoma is a very rare form of large B cell non-Hodgkin’s lymphoma, characterised by the presence of lymphoma cells in the lumina of small vessels only, particulary in the capillaries. We report a 54 year-old female non-smoker, admitted to hospital for further examination of a four month long clinical condition involving high fever, night sweats, unqualified weight loss and progressive dyspnea. Patient’s temperature was 38.5 oC, pulse 100/min and respiratory 22 cycles/min. Patient’s haemoglobin was 9.4 g/dL, she had leukocytosis, elevated LDH and arterial blood gas analysis with moderate hypoxaemia (FiO2 1 l/m: PaO2-63.6 mm Hg). Chest X-ray revealed diffuse interstitial changes. All the possible causes of unknown origin fever were excluded. Diagnosis was made through lung biopsy and treatment with combined chemotherapy and rituximab was prescribed leading to a 48 hours clinical remission. We present this case to show how difficult this diagnosis can be and how a good response to therapy is possible. Rev Port Pneumol 2008; XIV (6): 857-868

Intravascular pulmonary lymphoma with good response to treatment. A case report

Intravascular lymphoma is a very rare form of large B cell non-Hodgkins lymphoma, characterised by the presence of lymphoma cells in the lumina of small vessels only, particularly in the capillaries. We report a 54 year-old female non-smoker, admitted to hospital for further examination of a four month long clinical condition involving high fever, night sweats, unqualified weight loss and progressive dyspnea. Patients temperature was 38.5 degrees C, pulse 100/min and respiratory 22 cycles/min. Patients haemoglobin was 9.4 g/dL, she had leukocytosis, elevated LDH and arterial blood gas analysis with moderate hypoxaemia (FiO2 1l/m: PaO2-63.6 mm Hg). Chest X-ray revealed diffuse interstitial changes. All the possible causes of unknown origin fever were excluded. Diagnosis was made through lung biopsy and treatment with combined chemotherapy and rituximab was prescribed leading to a 48 hours clinical remission. We present this case to show how difficult this diagnosis can be and how a good response to therapy is possible.

Biologia do cancro do pulmão: conceitos actuais

RESUMO No presente artigo de revisao o autor relata os conhecimentos actuais sobre a biologia celular e molecular do cancro do pulmao, relacionandoos, sempre que possivel, com as respectivas implicacoes diagnosticas, prognosticas e terapeuticas. REV PORT PNEUMOL 2002; VIII (6): 655-679

Angiosarcoma of the lung

Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis.