PDF(Pubmed)
Abstract：
BACKGROUND: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients.
METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS).
RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient\'s or investigator\'s decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study.
CONCLUSIONS: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.
METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS).
RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient\'s or investigator\'s decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study.
CONCLUSIONS: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.
摘要：
背景：对于因II/III期胃癌而接受胃切除术的东亚患者，S-1已被证明是一种有效的辅助治疗选择。我们进行了I/II期研究来评估可行性，高加索患者胃和食管胃结合部腺癌（EGJ）R0切除术后在辅助环境中给予S-1的耐受性和疗效。
方法：在这个单一队列中，开放标签，I/II期试验，我们纳入了局部晚期胃腺癌或EGJ患者,这些患者接受了有或没有新辅助治疗的R0切除术.一个治疗周期包括口服S-1（30mg/m²bid）14天。每3周重复一个周期,共18个周期(54周)。主要终点是可行性和耐受性。根据常见毒性标准不良事件4.0标准评价安全性。次要终点是一年无复发生存率，无复发生存期（RFS）和总生存期（OS）。
结果：在2015年10月至2018年2月之间，在12个德国中心招募了32例患者，30例开始了辅助研究治疗。17例患者完成全部18个周期。两名患者因不良事件（AE）终止研究治疗，7由于患者或研究者的决定，4由于在辅助治疗期间复发或远处转移。9例患者的剂量水平降至25mg/m²，1例患者的剂量为20mg/m²。在完成所有18个周期的患者中，5用减少的S-1剂量这样做。记录的≥3级AE为中性粒细胞减少症，腹泻,呕吐,多发性神经病,掌足红感觉障碍和皮疹。在7例患者中观察到严重的AE。RFS中位数为32.2个月。一年无复发生存率为77%。在研究结束时，关于OS的数据仍然为时过早。
结论：S-1辅助治疗一年对于在R0切除后诊断为胃腺癌或EGJ癌的高加索患者是一种可行且安全的治疗选择。
方法：在这个单一队列中，开放标签，I/II期试验，我们纳入了局部晚期胃腺癌或EGJ患者,这些患者接受了有或没有新辅助治疗的R0切除术.一个治疗周期包括口服S-1（30mg/m²bid）14天。每3周重复一个周期,共18个周期(54周)。主要终点是可行性和耐受性。根据常见毒性标准不良事件4.0标准评价安全性。次要终点是一年无复发生存率，无复发生存期（RFS）和总生存期（OS）。
结果：在2015年10月至2018年2月之间，在12个德国中心招募了32例患者，30例开始了辅助研究治疗。17例患者完成全部18个周期。两名患者因不良事件（AE）终止研究治疗，7由于患者或研究者的决定，4由于在辅助治疗期间复发或远处转移。9例患者的剂量水平降至25mg/m²，1例患者的剂量为20mg/m²。在完成所有18个周期的患者中，5用减少的S-1剂量这样做。记录的≥3级AE为中性粒细胞减少症，腹泻,呕吐,多发性神经病,掌足红感觉障碍和皮疹。在7例患者中观察到严重的AE。RFS中位数为32.2个月。一年无复发生存率为77%。在研究结束时，关于OS的数据仍然为时过早。
结论：S-1辅助治疗一年对于在R0切除后诊断为胃腺癌或EGJ癌的高加索患者是一种可行且安全的治疗选择。
