Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group

Background: The aim of this study was to determine the efficacy of the EAP regimen (etoposide, adriamycin and cisplatin) followed by the Machover schedule (fluorouracil and folinic acid) given as adjuvant treatment to patients with poor prognostic factors (N+ or T3/4). Patients and methods: Before randomisation, the subjects were stratified on the basis of node involvement (N+ or N-) and the time from surgery to randomisation (less than or equal to21 days or >22 days). The surgical procedures for sub-total or total gastrectomy with D2 dissection were standardised among the participating centres. Results: Between December 1992 and December 1997, 274 patients were enrolled: 137 in the treatment arm and 137 in the control arm. The majority of the patients (90%) were N+. After a median follow up of 66 months (range 2-83), the 5-year overall survival (OS) was 52% in the treatment arm and 48% in the control arm [hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65-1.34]; the 5-year disease-free survival (DFS) was 49% and 44%, respectively (HR: 0.83; 95% CI 0.59-1.17). Among the patients with N-/N+ (1-6), the 5-year OS was 61% in the treatment group and 60% in the control group, in those with N+ (1-6), it was 42% and 22%. The treatment was completed by 87% of patients. Drug-related grade 3/4 WHO toxicities included leukopenia (21%), nausea and vomiting (14%), mucositis (9%), neutropenia (3%) and thrombocytopenia (2%). There were two deaths due to sepsis, Conclusions: Although our results are not statistically significant, there was a limited relative risk reduction in the patients receiving adjuvant therapy (17% in DFS and 7% in OS). The data suggest that D2 surgery may have a favourable impact on OS.