Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, Goto M
Department of Surgery, Cancer Institute Hospital, Tokyo, Japan.
Lancet. 1999 Jul 24;354(9175):273-7. doi: 10.1016/s0140-6736(99)01048-x.
To study the survival benefit of adjuvant chemotherapy in gastric cancer, seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer.
579 patients were enrolled in the study, stratified by disease stage (T1, n=188; T2, n=323), and allocated randomly adjuvant chemotherapy or no further treatment. 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible. Six cases were excluded because they did not fulfill the entry criteria. The treatment group had intravenous mitomycin (1.4 mg/m2) and fluorouracil (166.7 mg/m2) twice weekly for 3 weeks after surgery, and oral UFT (uracil plus tegafur, 300 mg daily) for 18 months. Analyses were by intention to treat.
No serious toxic effects were observed in the treatment group. At median follow-up of 72 months, 59 patients in the control group and 47 in the treatment group had died. There was no significant difference in survival between the groups (5-year survival 82.9% control vs 85.8% treated; hazard ratio 0.738 [95% CI 0.498-1.093]). 5-year survival of patients with T1 (mucosal or submucosal) cancer in the control and treatment groups was 94.9% versus 92.0%, and that of patients with T2 (muscularis propria or subserosa) cancer was 76.9% versus 83.0%. However, a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response.
There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer (T1 and T2) after curative gastrectomy. Patients with T1 cancer can be excluded from future trials, because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy.
为研究辅助化疗对胃癌患者的生存获益情况，日本的7个癌症中心开展了一项针对肉眼可见浆膜阴性胃癌根治性胃切除术后辅助化疗的III期临床试验。
579例患者入组本研究，按疾病分期分层（T1期，n = 188；T2期，n = 323），随机分配接受辅助化疗或不再接受进一步治疗。治疗组288例中的285例以及对照组291例中的288例符合条件。6例因未满足纳入标准而被排除。治疗组在术后每周两次静脉注射丝裂霉素（1.4 mg/m²）和氟尿嘧啶（166.7 mg/m²），共3周，随后口服优福定（尿嘧啶加替加氟，每日300 mg），持续18个月。分析采用意向性治疗。
治疗组未观察到严重毒性作用。在中位随访72个月时，对照组59例患者死亡，治疗组47例患者死亡。两组间生存率无显著差异（5年生存率：对照组82.9%，治疗组85.8%；风险比0.738 [95%可信区间0.498 - 1.093]）。对照组和治疗组T1期（黏膜或黏膜下层）癌症患者的5年生存率分别为94.9%和92.0%，T2期（固有肌层或浆膜下层）癌症患者的5年生存率分别为76.9%和83.0%。然而，对T1和T2亚组的异质性和交互作用检验显示，药物反应方面无显著差异。
对于肉眼可见浆膜阴性胃癌（T1和T2）患者，根治性胃切除术后采用这种辅助治疗方案未带来生存获益。T1期癌症患者可排除在未来试验之外，因为单纯根治性手术已产生非常好的生存率，似乎无需辅助治疗。
