Current status and future perspectives of post-operative adjuvant therapy for gastric carcinoma

Abstract

The clinical benefit of post-operative adjuvant immunochemotherapy for survival of patients with gastric carcinoma is unclear, although a number of prospective randomized controlled studies have been conducted. The current status and future perspectives of post-operative adjuvant chemotherapy in gastric carcinoma have been evaluated in terms of survival benefit. The results of randomized clinical studies vary in accordance with the regimen and sample size. A meta-analysis, however, indicated a survival benefit in patients treated with post-operative adjuvant chemotherapy including mitomycin, anthracyclines, cyclophosphamide, alkylating agents and 5-fluorouracil (odds ratio: 0.8 to approximately 0.82, 95% CI<1.0). The survival benefit was observed in patients with stage II and stage III gastric carcinoma, but not those with stage I. Further, the survival benefit in node-positive and high histological grade subgroups was superior to that in node-negative and low histological grade subgroups. Although combination therapy with mitomycin, 5-fluorouracil and non-specific immunomodulators, such as PSK and OK-432, appeared to improve overall survival without immunomodulators, the survival effect of immunomodulators is still not clear. There are several possible reasons why the survival benefit of adjuvant chemotherapy or immunochemotherapy is small and marginal compared to surgery alone: (i) low efficacy of the chemotherapy regimen; (ii) small sample size; and (iii) differences in chemosensitivity of treated patients based on genetic background. The determination of subgroups responsive to chemotherapy and the development of a rationale-based and molecular-targeted chemotherapy are required to clearly demonstrate whether there is a survival benefit of post-operative adjuvant chemotherapy in gastric carcinoma.