Kato Takehiro, Uehara Keisuke, Maeda Atsuyuki, Sakamoto Eiji, Hiramatsu Kazuhiro, Takeuchi Eiji, Goto Hidenari, Tojima Yuichiro, Yatsuya Hiroshi, Nagino Masato
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Cancer Chemother Pharmacol. 2015 Jun;75(6):1281-8. doi: 10.1007/s00280-015-2752-5. Epub 2015 May 1.
We previously showed that S-1 after curative resection of colorectal liver metastasis had acceptable toxicity and a high rate of completion of therapy in a prospective phase II trial. We here reported the primary endpoint of disease-free survival (DFS).
Between October 2008 and August 2010, 60 patients were eligible for this study and received S-1 for 28 days followed by a 2-week rest period. Treatment was started within 8 weeks after surgery and repeated for eight cycles.
Median follow-up was 41 months. Among 60 patients, 45 had solitary metastasis, and the median maximum tumor diameter was 2.6 cm. The 3-year DFS and overall survival were 47.4 and 80.0 %, respectively. Recurrences developed in 31 patients, with the remnant liver the most common site (19 patients). Multivariate analysis showed that positive lymph node metastasis around the primary site (p = 0.013) and early liver metastasis (synchronous disease or metachronous disease within 12 months) (p = 0.041) were independent poor prognostic factors for DFS. Patients having both risk factors had a significantly worse DFS than those without these risk factors (p < 0.001). Early liver metastasis was an independent indicator of early recurrence within 1 year.
S-1 after curative liver resection yielded promising survival in patients with a low tumor burden. Outcome in patients having both positive lymph node metastasis around the primary site and early liver metastasis was much worse than in patients without these conditions; therefore, they might warrant more aggressive therapy.
我们之前在一项前瞻性II期试验中表明，结直肠癌肝转移根治性切除术后使用S-1具有可接受的毒性和较高的治疗完成率。我们在此报告无病生存期（DFS）这一主要终点。
2008年10月至2010年8月期间，60例患者符合本研究条件，接受S-1治疗28天，随后休息2周。治疗在术后8周内开始，并重复8个周期。
中位随访时间为41个月。60例患者中，45例为孤立性转移，中位最大肿瘤直径为2.6厘米。3年DFS和总生存率分别为47.4%和80.0%。31例患者出现复发，残留肝脏是最常见的复发部位（19例）。多因素分析显示，原发部位周围阳性淋巴结转移（p = 0.013）和早期肝转移（同步疾病或12个月内的异时性疾病）（p = 0.041）是DFS的独立不良预后因素。同时具有这两个危险因素的患者DFS明显差于无这些危险因素的患者（p < 0.001）。早期肝转移是1年内早期复发的独立指标。
根治性肝切除术后使用S-1在肿瘤负荷低的患者中产生了有前景的生存率。原发部位周围有阳性淋巴结转移且有早期肝转移的患者的预后比无这些情况的患者差得多；因此，他们可能需要更积极的治疗。
