Adjuvant chemotherapy for gastric cancer in Japan: global and Japanese perspectives

Abstract

Adjuvant therapy for gastric cancer after surgical resection has been under clinical investigation for decades. However, up until now, consistent and concrete evidence has not been generated either in Japan or other countries in favor of adjuvant therapy in terms of survival compared to surgery alone. Meta-analyses reported from Western countries have shown either no or borderline benefit for chemotherapy after surgical resection of gastric cancer. A recent trial showed significant benefit for chemoradiotherapy. However, Japanese specialists believe that their perspectives are different from those in the West due to the following: (1) gastric cancer incidence is several times higher in Japan; (2) more stringent screening programs are emphasized in Japan, thus baseline conditions of cancer patients are different; (3) specific operative techniques are used; and (4) Japanese surgeons have probably acquired additional experience in gastric cancer resection techniques. From the 1960s to the 1980s first mitomycin (MMC) and, later, a combination of oral fluorinated pyrimidines (o-FP) and MMC showed improved survival benefit in Japan compared to surgery alone. However, in the late 1980s, an expert group re-examined the results of previous trials, questioned them, and suggested fresh trials. Since then, the Japanese Clinical Oncology Group (JCOG) has conducted relevant trials to re-examine the effect of MMC and/or o-FP as adjuvant chemotherapy. The results of trials JCOG 8801 and JCOG 9206 have already been reported, and the accrual of patients for another trial (NSAS-GC trial) has just been completed. A pooled analysis of the two preceding trials showed a borderline survival benefit for o-FP compared to surgery alone. If o-FP treatment shows a 5% difference in survival benefit in the NSAS-GC trial, a meta-analysis of the three trials would probably reveal overall significant results. In conclusion, this therapy could become the standard adjuvant treatment regimen for gastric cancer patients after curative resection in Japan.

Recent results of therapy for scirrhous gastric cancer

“…This study demonstrated that the adjuvant UFT chemotherapy signifi cantly prolonged the overall survival of the patients. 28 In contrast to the NSAS-GC01 trial, the Japan Clinical Oncology Group (JCOG) 9206-2 trial could not show a survival benefi t of adjuvant chemotherapy with cisplatin plus 5-FU followed by UFT for resected serosalpositive (T3 and T4) gastric cancer. 29 The effi cacy of UFT was infl uenced by the status of enzymes involved in 5-FU metabolism such as thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD).…”

UFT (Tegafur and Uracil) as Postoperative Adjuvant Chemotherapy for Solid Tumors (Carcinoma of the Lung, Stomach, Colon/Rectum, and Breast): Clinical Evidence, Mechanism of Action, and Future Direction

“…50,51 This study failed to show a signifi cant survival benefi t of postoperative adjuvant chemotherapy with MF plus UFT for T1-2 gastric cancer, but it did show a trend in favor of the adjuvant chemotherapy Recent meta-analyses of RCTs of adjuvant chemotherapy conducted in Japan showed a small or borderline survival benefi t of postoperative adjuvant chemotherapy, especially UFT-containing chemotherapy, for resected gastric cancer. 53,54 More recently, a meta-analysis of centrally randomized adjuvant UFT (Table 5). In the meta-analysis, a total of 1503 patients were analyzed, and there proved to be a signifi cant survival benefi t for the postoperative adjuvant UFT treatment (HR = 0.70 [95% CI: 0.54-0.89] and P = 0.01).…”

“…39 Therefore, it is generally accepted in Japan that surgery alone remains a standard therapy for respectable gastric cancer. 37,38 As UFT is an active and well-tolerated chemotherapeutic agent for gastric cancer, 47 a series of RCTs of adjuvant chemotherapy containing UFT for resected gastric cancer have been conducted by the Japan Clinical Oncology Group (JCOG) [48][49][50][51][52] and other cooperative study groups in Japan 37 (Table 2). In the JCOG-8801 trial, a total of 579 patients with curatively resected gastric cancer (T1 with nodal metastasis or T2 disease) were randomly assigned to the surgery-alone group or surgery followed by the chemotherapy group; chemotherapy consisted of intravenous chemotherapy (mitomycin C [MMC] plus 5-FU, MF) followed by oral UFT administration.…”

Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer

“…Significant geographic variation exists, with high-risk areas such as Japan, Eastern Asia, and Central and South America (Terry et al, 2002;Sakamoto et al, 2004). The incidence is relatively low in the United States; however, gastric cancer is a significant cause of morbidity and mortality, with 23 000 cases per year, resulting in 12 000 annual deaths (Jemal et al, 2004).…”