Mitomycin therapy in gastric cancer.

Adenocarcinoma of the stomach remains a significant cause of mortality worldwide. The majority of patients present with stage III or IV disease, negating surgery as a curative option. Numerous drugs have been tested over the past 2 decades in single-agent and combination chemotherapy trials. Given by intravenous bolus, mitomycin has induced responses as high as 63% and as low as 24% in patients with various gastrointestinal malignancies. Mitomycin has also demonstrated efficacy when given in combination with doxorubicin and in the three-drug regimen FAM (5-fluorouracil/doxorubicin/mitomycin). FAM has been explored in multiple phase II and III trials and has become the standard with which many new combinations are compared. Compared with other doxorubicin-containing regimens, it has demonstrated the longest median survival (29.5 weeks) and the lowest incidence of severe toxicity. The addition of semustine or leucovorin to FAM has yielded responses comparable with those attained by FAM alone. In Japan, where treatment of gastric cancer has been more successful, possibly due to earlier diagnosis and more aggressive surgical approaches, mitomycin has been given intraperitoneally during surgery and postoperatively in combination with fluorinated pyrimidines or other agents. Mitomycin will undoubtedly play a role in the development of new approaches to the treatment of gastric cancer.