Prolongation of Skin Homograft Survival by Thalidomide

Abstract

Bronchial Carcinoma-Barran et al. BRfTfsH 687After more than two years there is one survivor out of four patients who underwent surgical resection after improving with preliminary treatment, whereas five out of eight having surgery without preliminary improvement survived two years and three are still alive. Again this difference could be pure chance. It could indicate that preliminary improvement on cytotoxic drugs was of no advantage or was harmful; but it was probably at least in part due to the fact that improvement with cytotoxic drugs occurred in patients with more rapidly growing and metastasizing tumours, which were therefore less amenable to curative resection.The pulmonary-artery-perfusion group was planned because of a remarkable result that occurred previously in one out of 25 patients treated in this way. He was a 52-year-old man who at thoracotomy was found to have an advanced oat-cell growth invading the main vessels. Three weeks later he was given one dose of 17.5 mg. of nitrogen mustard by drip into the right main pulmonary artery. The next day he felt much better, and five days later the chest x-ray picture showed marked reduction in the shadowing due to the growth. Two weeks later the x-ray appearance had returned to normal and bronchoscopy confirmed the apparent complete resolution of the neoplasm. Four further perfusions were carried out during the next year and he remained well and at work for this period. Early recurrence was first suspected after 16 months, and deep x-ray therapy was given after 20 months. He survived for two and a half years.One patient in the present series treated by pulmonary-artery perfusion with cyclophosphamide survived over 18 months, but this was a case of squamous-cell carcinoma and may well have been naturally slow-growing. There were no other responses worthy of remark.The place of cytotoxic-drug therapy in the treatment of carcinoma of the bronchus remains controversial. The present series suggests that in about 50% of patients the tumour will recede to some extent during high-dosage treatment with cyclophosphamide.Poulsen 's (1962, 1963) findings of a higher one-year survival rate in patients with operable squamous-cell carcinomas treated with pre-operative and post-operative cyclophosphamide than in a controlled group having surgery alone encourages further research on these lines in the early cases.With advanced disease the remissions are usually short, ranging from two to six months, but often they are worth while from the point of view of relief of distressing symptoms. It remains to be seen whether better results can be obtained with maintenance therapy or the combination of two or more different agents, and whether, when combined with x-ray therapy, summation or sensitizing effects can be obtained. SummaryNinety-seven patients with bronchial carcinoma were treated with nitrogen mustard or cyclophosphamide. Of those treated with cyclophosphamide 51% responded favourably as judged by the objective evidence, compared with 33 % of those receiving nitrogen...

Estudo comparativo dos efeitos da talidomida, da ciclosporina e do diclofenaco na sobrevida de aloenxertos cutâneos em coelho

“…As pesquisas com coração, iniciadas em 1989, mostraram que a talidomida, isolada ou em associação com a ciclosporina, prolongava a sobrevida de transplantes cardíacos heterotópicos 9. A literatura referente ao efeito da talidomida em aloenxertos de pele é controversa. Hellman et al (1965) observaram que a talidomida retardou a rejeição de aloenxertos, principalmente quando estes haviam sido incubados com a droga ou quando os animais doadores, além dos receptores, também foram tratados com talidomida 17 . Vogelsang et al (1988) relataram aumento na sobrevida de transplantes de pele com a administração da talidomida duas vezes ao dia 10 .…”

“…Neste trabalho, o diclofenaco foi introduzido como controle para avaliar os efeitos antiinflamatórios da talidomida. Cabe ressaltar o papel antiinflamatório pelo qual a talidomida destaca-se em relação a outros medicamentos 8,17,18 . Por este motivo, ela continua como medicamento de escolha em hanseníase.…”

“…Por este motivo, ela continua como medicamento de escolha em hanseníase. Por outro lado, existe ainda o efeito imunodepressor que pode associar-se na farmacocinética da talidomida e que não tem sido apontado em outros antiinflamatórios não-esteróides 8,17,18 . Neste sentido, coube a comparação entre talidomida e diclofenaco.…”

“…O presente trabalho mostrou que a talidomida, como droga isolada, prolongou a sobrevida dos aloenxertos, em relação ao grupo controle, em cerca de 24 horas, o que concorda com relatos anteriores 9,17 . Estatisticamente, seu efeito foi comparável ao do antiinflamatório diclofenaco.…”

“…O padrão de rejeição observado nos grupos de animais tratados com ciclosporina já havia sido descrito por Hellmann et al (1965) com o uso da talidomida em camundongos 17 . A necrose foi mais lenta em alguns animais, ocorrendo em focos, com persistência de ilhas de tecido viáveis.…”