Adjuvant therapy of gastric cancer using an array of cytotoxic agents, administered singly or in combination, has been widely tested within the last 3 decades. Although chemotherapy alone following gastric resection has failed to consistently produce a clinically significant survival benefit among patients studied in the Western world (8,9), several randomized trials have reported positive results, but none so convincing as to establish the treatment protocol studied as standard of care (10–14).

In 1982, the Gastrointestinal Tumor Study Group (10) reported the results of a clinical trial in which 142 patients who had undergone curative gastric resection for adenocarcinoma were randomized to receive adjuvant methyl-CCNU and 5-fluorouracil (5-FU) or close observation only. After a median follow-up period of 4 years, a survival advantage appeared to be associated with the adjuvant therapy (p <0.03). Median survival for the control patients was 33 months, whereas it was estimated to be in excess of 4 years in the treated group. Unfortunately, these favorable results were not confirmed in trials with the same agents subsequently reported from the Veterans Administration Surgical Oncology Group (15) and the Eastern Cooperative Oncology Group (16).

In 1991, Estape et al. (12) published the outcome of their randomized trial of adjuvant mitomycin C. Thirty-three patients received the drug and 37 patients were managed with surgery only. After 5 years of follow-up, the actuarial survival curve was statistically in favor of the adjuvant therapy (p <0.001), a benefit that was sustained at 10 years (p <0.01). Seventeen of 33 treated patients (52%) and 6 of 37 untreated patients (16%) were alive at 10 years. Patients with stage T3N0M0 disease benefited most. The most frequent site of relapse was the peritoneal cavity.

Neri et al. (13,14) studied the subset of resected patients with positive nodes. The experimental group received adjuvant epidoxorubicin, 5-FU, and leucovorin. At 3 years, 25% of treated patients but only 13% of control patients were alive. At that point, the ...