A PHASE-II STUDY OF MITOMYCIN-C AND ORAL ETOPOSIDE FOR ADVANCED ADENOCARCINOMA OF THE UPPER GASTROINTESTINAL-TRACT

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor w ith evidence for phase-specific and schedule-dependent activity. Patie nts and method: Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) b olus mitomycin C 6 mg/m(2) on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d liquid) were administered days 1 to 10 extending to 14 days in subsequent cou rses if absolute neutrophil count >1.5 x 10(9)/l on day 14 of first co urse, for up to six courses. Results: Twenty-six patients were assesse d for response of whom 12 had measurable disease and 14 evaluable dise ase. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable diseas e and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine pat ients experienced leucopenia (seven grade II and two grade III). Nause a and vomiting (eight grade II, one grade III), fatigue (eight grade I I, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced uppe r gastrointestinal adenocarcinoma. Further studies using protracted sc hedules of etoposide both orally and as infusional treatment should be developed.