S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial
S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial
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DOI：
10.1016/s1470-2045(08)70035-4
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发表时间：
2008-03-01
期刊：
影响因子：
51.1
通讯作者：
Takeuchi, Masahiro
中科院分区：
文献类型：
--
作者：
Koizumi, Wasaburo;Narahara, Hiroyuki;Takeuchi, Masahiro
背景替吉奥联合顺铂治疗晚期胃癌的I/II期临床试验已获得良好的反应，且治疗耐受性良好。在这项S-1加顺铂与S-1在胃癌治疗中的随机对照试验（SPIRITS）中，我们旨在验证S-1加顺铂治疗晚期胃癌患者的总生存率优于S-1单药治疗。方法在这项III期试验中，2002年3月26日至2004年11月30日期间入组了未经化疗的晚期胃癌患者，在日本的38个研究中心，随机分配至S-1+顺铂组或S-1单药组。在分配至S-1+顺铂组的患者中，口服S-1（40-60 mg，取决于患者的体表面积），每日2次，连续3周，第8天静脉注射60 mg/m2顺铂，随后停药2周，在5周周期内。分配至S-1单独给药组的受试者在6周周期内接受相同剂量的S-1，每日两次，连续4周，随后停药2周。主要终点是总生存期。次要终点为无进展生存期、应答者比例和安全性分析，通过意向治疗进行分析。该试验在ClinicalTrials.gov注册，编号NCT 00150670。结果305例患者入组; 7例患者不合格或撤回知情同意，因此，148例患者被分配至S-1+顺铂组，150例患者被分配至S-1单药组。分配至S-1+顺铂组的患者中位总生存期（13.0个月[IQR 7.6-21.91]）显著长于分配至S-1单药组的患者（11.0个月[5.6-19.81;死亡风险比，0.77; 95% CI 0.61-0.98; p=0.04）。接受S-1联合顺铂治疗的患者的无进展生存期显著长于接受S-1单药治疗的患者（中位无进展生存期6.0个月[3.3-12.91 vs 4.0个月[2.1-6.8]; p< 0.0001）。此外，在87例分配S-1+顺铂的靶肿瘤患者中，1例患者完全缓解，46例患者部分缓解，即总计54%（范围43-65）。在106例仅分配S-1的靶肿瘤患者中，1例患者完全缓解，32例患者部分缓解，即总计31%（23-41）。与单用S-1组相比，S-1+顺铂组记录到更多的3级或4级不良事件，包括白细胞减少症、中性粒细胞减少症、贫血、恶心和厌食。两组均无治疗相关性死亡。解读替吉奥联合顺铂有望成为晚期胃癌患者的标准一线治疗方案。
Background Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone.Methods In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled betweeen March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670.Findings 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.91) than in those assigned to S-1 alone (11.0 months [5.6-19.81; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.91 vs 4.0 months [2.1-6.8]; p< 0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group.Interpretation S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.