Kinoshita Taira, Sasako Mitsuru, Sano Takeshi, Katai Hitoshi, Furukawa Hiroshi, Tsuburaya Akira, Miyashiro Isao, Kaji Masahide, Ninomiya Motoki
Department of Surgical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Gastric Cancer. 2009;12(1):37-42. doi: 10.1007/s10120-008-0496-1. Epub 2009 Apr 24.
The prognosis of scirrhous gastric cancer remains poor despite extended surgery or adjuvant or neoadjuvant chemotherapy. A pilot study of S-1 (TS-1; Taiho Pharmaceutical, Tokyo, Japan), an oral 5-fluorouracil derivative, for neoadjuvant chemotherapy unexpectedly showed good response and a promising effect on survival. Therefore, the Japan Clinical Oncology Group conducted a phase II trial to confirm the efficacy of S-1 for neoadjuvant chemotherapy against resectable scirrhous gastric cancer.
Patients were eligible if they had typical scirrhous gastric cancer invading more than half of the stomach, and resectable disease confirmed by laparoscopic staging. The treatment schedule consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 (100-120 mg/body per day), followed by radical surgery.
Fifty-five eligible patients were registered. Three completed only one course of the neoadjuvant chemotherapy, whereas 52 completed two courses. Toxicity was acceptable, with a few grade 3 (5.5%) events, but no grade 4 adverse events. The response rate was 32.6% in 43 evaluable patients. Of the 55 patients, 2 refused operation, 1 developed lung metastasis, and 52 underwent laparotomy. The curative resection rate was 80.8%, with acceptable morbidity and no mortality. The survival curve at 2 years' follow up showed a better survival rate than that of the historical controls, but did not reach the expected survival rate.
S-1 neoadjuvant chemotherapy appeared feasible and showed positive effects against scirrhous gastric cancer; however, the survival rate with S-1 did not reach the expected rate required when selecting an agent for a phase III trial to confirm the effectiveness of neoadjuvant chemotherapy against scirrhous gastric cancer.
尽管进行了扩大手术或辅助或新辅助化疗，硬癌型胃癌的预后仍然很差。一项关于口服5-氟尿嘧啶衍生物S-1（TS-1；日本东京大鹏药品工业株式会社）用于新辅助化疗的试点研究意外地显示出良好的反应以及对生存有显著效果。因此，日本临床肿瘤学会开展了一项II期试验，以证实S-1用于可切除硬癌型胃癌新辅助化疗的疗效。
患者符合条件需患有典型的侵犯胃超过一半的硬癌型胃癌，且经腹腔镜分期确认疾病可切除。治疗方案包括两个疗程（每个疗程为4周给药和2周停药）的S-1（每天100 - 120毫克/体），随后进行根治性手术。
登记了55名符合条件的患者。3名患者仅完成了一个疗程的新辅助化疗，而52名患者完成了两个疗程。毒性反应可接受，少数为3级事件（5.5%），但无4级不良事件。43名可评估患者的缓解率为32.6%。55名患者中，2名拒绝手术，1名发生肺转移，52名接受了剖腹手术。根治性切除率为80.8%，发病率可接受且无死亡病例。2年随访的生存曲线显示生存率优于历史对照，但未达到预期生存率。
S-1新辅助化疗似乎可行，对硬癌型胃癌显示出积极效果；然而，S-1治疗的生存率未达到选择用于III期试验以证实新辅助化疗对硬癌型胃癌有效性的药物时所需的预期率。
