S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102)
S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102)
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DOI：
10.1007/s10147-015-0943-z
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发表时间：
2016-08-01
影响因子：
3.3
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
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作者：
Miyamoto, Yuji;Tsuji, Akihito;Maehara, Yoshihiko
在日本，S-1和伊立替康联合化疗是转移性结直肠癌（mCRC）的标准治疗之一。然而，几乎没有替代的实用二线疗法。我们进行了一项II期临床试验，以评估S-1和伊立替康联合贝伐珠单抗作为奥沙利铂难治性mCRC二线治疗的疗效和安全性。口服S-1，剂量为80 mg/m2，每日两次，持续2周，随后停药1周。第1天给予伊立替康150 mg/m2和贝伐珠单抗7.5 mg/kg。主要终点为无进展生存期（PFS），共纳入37例患者，分别评估了34例和36例患者的反应和安全性。总体缓解率为20.6%（95%置信区间[CI] 8.7-37.9），疾病控制率为76.5%（95% CI 58.8-89.3）。中位PFS为5.6个月（95% CI 3.8-7.0）。中位总生存期为16.4个月（95%CI 8.1-20.0）。最常见的3/4级不良事件包括中性粒细胞减少（25.0%）、厌食（22.2%）、贫血（16.7%）和疲乏/不适（16.7%）。贝伐珠单抗最常见的3/4级特别关注的不良事件是高血压（30.6%）。结果表明，S-1和伊立替康联合贝伐珠单抗作为奥沙利铂难治性mCRC患者的二线化疗有效且耐受。
Combination chemotherapy with S-1 and irinotecan is one of the standard treatments for metastatic colorectal cancer (mCRC) in Japan. However, there are few alternative practical second-line therapies. We conducted a phase II trial to evaluate the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab as a second-line treatment for oxaliplatin-refractory mCRC.Patients with mCRC who were previously treated with oxaliplatin-containing regimens were enrolled. Oral S-1 at a dose of 80 mg/m(2) was administered twice daily for 2 weeks, followed by a 1-week drug-free interval. Irinotecan at a dose of 150 mg/m(2) and bevacizumab at a dose of 7.5 mg/kg were administered on day 1. The primary endpoint was progression-free survival (PFS).Thirty-seven patients were enrolled, and 34 and 36 patients were assessed for response and safety, respectively. The overall response rate was 20.6 % (95 % confidence interval [CI] 8.7-37.9), and the disease control rate was 76.5 % (95 % CI 58.8-89.3). The median PFS was 5.6 months (95 % CI 3.8-7.0). The median overall survival was 16.4 months (95 % CI 8.1-20.0). The most common grade 3/4 adverse events included neutropenia (25.0 %), anorexia (22.2 %), anemia (16.7 %), and fatigue/malaise (16.7 %). The most common grade 3/4 adverse event of special interest for bevacizumab was hypertension (30.6 %). One treatment-related death caused by gastrointestinal bleeding occurred.The findings suggest that the combination of S-1 and irinotecan plus bevacizumab is effective and tolerable as second-line chemotherapy for patients with oxaliplatin-refractory mCRC.