Chapter 99: Multimodality Therapy of Gastric Cancer: Eastern Experience

INTRODUCTION

Several bodies of evidence both from the West and the East currently recommend that some form of adjuvant therapy should be delivered in addition to surgery in patients with potentially curable advanced gastric cancer. Progress in surgical technique to dissect cancer with wide resection margin may have reached a plateau,¹ and development of perioperative adjuvant therapy is the only way to improve the outcome. This chapter describes the history and recent advances in the multimodality treatment in the Far East where the incidence of this disease remains high.

POSTOPERATIVE ADJUVANT CHEMOTHERAPY

Rationale and Brief History

Surgeons are capable of removing macroscopic disease by gastrectomy, and could additionally remove occult microscopic lymphatic spread through en bloc nodal dissection. However, cancer cells that entered the blood stream or were exfoliated from the serosal surface and shed into the peritoneal cavity could develop into recurrences. It is well documented that micrometastases are more vulnerable to chemotherapy than gross metastases, and adjuvant therapy after surgical resection could theoretically be recommended. Administration of intravenous mitomycin and/or oral fluoropyrimidines became the community standard in Japan after the positive result of a phase III trial with surgery alone as a control.² However, the study, conducted between 1964 and 1973, was found later to be of insufficient quality to merit universal recognition. Since the late 1980s, therefore, several randomized trials comparing adjuvant chemotherapy with surgery alone were conducted by the Japan Clinical Oncology Group (JCOG), a study group funded by the Japanese government, which consistently failed to prove a survival benefit. A history before the current standard of care was established has been summarized in Table 99-1. Some trials failed due to inclusion criteria by which only patients with relatively early-stage cancer were deemed eligible.^3,4 One of these trials was criticized as underpowered because it failed to detect marginal benefit that might have existed.⁴ Another trial explored a treatment that was eventually found to be unsuitable both in terms of efficacy and feasibility.⁵ The final attempt during this era was a pivotal phase III trial exploring high-dose UFT (360 mg/m²/day) for 16 months among patients with node-positive pT2~3 cancer.⁶ Unfortunately, the accrual for this study was extremely poor due to rarity of the disease that fell into these disease categories and small number of institutions that were invited to participate, and the trial had to be stopped well before the planned number of patients was enrolled.