La Gastroprotezione Nel Paziente Oncologico: Approccio Razionale, Ruolo Dei Farmaci Antisecretori Ed Eventuali Ulteriori Prospettive in Oncologia

In view of the large number of cancer patients treated with FANS and/or corticosteroids for long periods of time, Authors discuss how the use of antisecretory drugs for gastroprotection has become common practice in spite of the lack of clear scientific evidence. The paper analyses the principal mechanisms of gastrotoxicity of FANS, essentially associated with the inhibition of prostaglandins and consequent reduction of the secretion of mucous and bicarbonate. It also discusses the numerous controlled trials evaluating the efficacy of ranitidine for gastroprotection versus placebo and versus the analogous synthetic substance, misoprostole, derived from prostaglandin E1. This analysis shows that misoprostole provides significant protection against both gastric and duodenal ulcers, whilst the antisecretory drug protects only against localised duodenal ulcer. The conclusion is that optimum protection against FANS is provided by misoprostole. In any case more than 30% of patients are destined to develop ulcerous or minor lesions for which treatment with antisecretory drugs is correct. After analysis of the available literature on the gastrotoxicity of corticosteroids, it is clear that this risk is real only for a small sub-population of patients (treated in dual therapy with FANS, for long periods, with high doses or in presence of ulcer anamnesis). It is not known in these cases whether prophylactic treatment is suitable, nor which would be the best prophylactic treatment. In other cases the problem does not arise since the number of patients developing ulcers is similar with corticosteroids treatment or with placebo. Some further interesting features of ranitidine compared to cimetidine (its better pharmacological profile due to the lack of side effects, lack of medullary depression, lack of interference with the immunological system, lack of antiandrogen effects) are also discussed. Particularly interesting is the lack of interference with cyclophosphamide metabolism, such interference having shown for cimetidine. Studies involving ranitidine treatment in association with Interleukin-2 for renal carcinoma and metastatic melanoma are also of interest although no statistically significant results are available as yet.