GASTROPROTECTION FOR ONCOLOGICAL PATIENTS - RATIONAL APPROACH, ROLE OF ANTISECRETORY AGENTS AND FUTURE OUTLOOK IN ONCOLOGY

In view of the large number of cancer patients treated with FANS and/o r corticosteroids for long periods of time, Authors discuss how the us e of antisecretory drugs for gastroprotection has become common practi ce In spite of the lack of clear scientific evidence. The paper analys es the principal mechanisms of gastrotoxicity of FANS, essentially ass ociated with the inhibition of prostaglandins and consequent reduction of the secretion of mucous and bicarbonate. It also discusses the num erous controlled trials evaluating the efficacy of ranitidine for gast roprotection versus placebo and versus the analogous synthetic substan ce, misoprostole, derived from prostaglandin El, This analysis shows t hat misoprostole provides significant protection against both gastric and duodenal ulcers, whilst the antisecretory drug protects only again st localised duodenal ulcer. The conclusion is that optimum protection against FANS is provided by misoprostole. In any case more than 30% o f 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 c lear that this risk is real only for a small sub-population of patient s (treated in dual therapy with FANS, for long periods, with high dose s or in presence of ulcer anamnesis). It is not known In these cases w hether prophylactic treatment is suitable, nor which would be the best prophylactic treatment. In other cases the problem does not arise sin ce the number of patients developing ulcers is similar with corticoste roids 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 effe cts) are also discussed. Particularly interesting is the lack of inter ference with cyclophosphamide metabolism, such interference having sho wn for cimetidine. Studies involving ranitidine treatment in associati on with Interleukin-2 for renal carcinoma and metastatic melanoma are also of interest although no statistically significant results are ava ilable as yet.