P I Reed, B J Johnston on behalf of the ECP-IM Intervention Study Group
Lady Sobell GI Unit, Wexham Park Hospital, Slough, SL2 4HL, UK. Correspondence to: P I Reed. Fax: (+44) 1753 511 835. E-mail: [email protected]
*This paper was an invited presentation at the 18th Annual Symposium of European Cancer Prevention Organisation (ECP): Precancerous lesions of the digestive tract held in Maastricht, The Netherlands, 12–14 October, 2000
Epidemiological studies have provided clues but not conclusive evidence as to the causation and therefore the prevention of gastric cancer and have established an association between poor nutrition, Helicobacter pylori infection and subsequent risk of distal intestinal-type gastric cancer. These facts were integrated into the Correa model of gastric carcinogenesis as initially described and subsequently modified by him. Thus, prospective studies testing the relationship between diet and precursor gastric lesions and in particular H. pylori eradication may represent a cost-effective means of preventing this disease.
The European Cancer Prevention Organisation (ECP) intestinal metaplasia (IM) intervention study was set up based on studies showing associations between low plasma ascorbic acid (AA) levels and lower vitamin C intake in patients with IM and also decreased intragastric AA levels in H. pylori infection (which return to normal on H. pylori eradication). The aim was to assess the effect of H. pylori eradication and prolonged vitamin C supplements (2 g daily for 3 years) on gastric IM. The study was approved by local research ethics committees and informed written consent obtained. Gastric biopsies were taken from patients attending for diagnostic upper gastrointestinal endoscopy for histology (four antral and four incisura) and rapid unease test (CLOtest™) for H. pylori. If IM was confirmed histologically patients were randomized according to H. pylori status, using a factorial double-blind design. H. pylori -negative patients received either vitamin C or placebo. H. pylori -positive patients were randomized on a 2:1 basis to receive active H. pylori eradication therapy with omeprazole 20 mg twice daily and clarithromycin 500 mg three times a day for 2 weeks or placebo and then to receive either active vitamin C supplementation or placebo for 3 years. The aim was to have 50%H. pylori -positive and 50%H. pylori -negative patients entering the supplementation phase. A 13 C-urea breath test was carried out to assess the outcome of eradication therapy.
Follow-up gastroscopy with biopsy was carried out 1 and 3 years after the start of the supplementation phase. All biopsies were assessed blind by an experienced histopathologist centrally. IM was typed and scored. Serum vitamin analyses were performed at entry, 12, and 36 months or on premature withdrawal. Patients were not given any dietary advice but were questioned at 3 monthly visits about intake of fruit and vegetable and vitamin supplements.
Six hundred and twelve patients were entered in the study (H. pylori positive n = 457;H. pylori -negative n = 155) and to date 260 have completed the study (H. pylori -positive 203;H. pylori -negative 57), which will end in April 2001. Fifty per cent of the H. pylori -positive patients were H. pylori -negative following the eradication treatment on entry into the supplementation phase. Interim analysis is not allowed for in the protocol so detailed results will only be available in late 2001.