Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Disaster and Comprehensive Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Cancer Chemother Pharmacol. 2018 Jun;81(6):1035-1041. doi: 10.1007/s00280-018-3568-x. Epub 2018 Apr 11.
The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment for patients with metastatic colorectal cancer.
Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade ≥ 3 diarrhea. Our hypothesis set 21% as a threshold incidence and 10% as an expected incidence from previous studies with one-sided alpha 0.05. The secondary endpoints included the relative dose intensity, progression-free survival, overall survival and other adverse events.
A total of 51 patients were enrolled. The incidence of grade ≥ 3 diarrhea was 15.7% (8/51). Other common grade ≥ 3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free survival and overall survival were 8.4 months (5.8-9.8) and 17.1 months (11.8-22.3).
The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.
本单臂二期临床试验的目的是评估与连续日给予 S-1 加伊立替康（标准 IRIS 方案）相比，隔日给予 S-1 加伊立替康是否能降低转移性结直肠癌二线治疗患者重度腹泻的发生率。
纳入一线奥沙利铂和氟嘧啶治疗失败的转移性结直肠癌患者。第 1 天静脉给予伊立替康（150mg/m）和贝伐珠单抗（5mg/kg）。隔日给予 S-1 口服，剂量为 40-60mg，每日两次。每 2 周重复一个周期。主要终点是 3 级及以上腹泻的发生率。我们假设发生率为 21%，这是基于既往单侧 α 0.05 的研究的阈值发生率，而预期发生率为 10%。次要终点包括相对剂量强度、无进展生存期、总生存期和其他不良反应。
共纳入 51 例患者。3 级及以上腹泻的发生率为 15.7%（8/51）。其他常见的 3 级及以上不良反应为中性粒细胞减少症、贫血、血小板减少症和乏力，发生率分别为 13.7%（7/51）、5.9%（3/51）、2.0%（1/51）和 5.9%（3/51）。伊立替康、贝伐珠单抗和 S-1 的相对剂量强度分别为 80.0%、86.8%和 77.7%。中位无进展生存期和总生存期分别为 8.4 个月（5.8-9.8）和 17.1 个月（11.8-22.3）。
对于接受转移性结直肠癌二线治疗的患者，隔日给予 S-1 给药并不能显著降低腹泻的发生率。
