Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Japan;
Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan.
Anticancer Res. 2022 May;42(5):2675-2681. doi: 10.21873/anticanres.15745.
BACKGROUND/AIM: The usefulness of angiogenesis inhibitors as second-line treatment after the progression of anti-epidermal growth factor receptor antibody drug-containing regimens for RAS wild-type metastatic colorectal cancer (mCRC) has not been fully investigated. Therefore, we conducted a phase II study to verify the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab (SIRB regimen) as second-line treatment for patients with oxaliplatin and cetuximab-refractory KRAS wild-type mCRC.
Patients with mCRC who had previously received oxaliplatin and cetuximab-containing regimen were eligible for this study. Patients were infused with bevacizumab 7.5 mg/kg and irinotecan 150 mg/m intravenously on day 1, whereas S-1 80 mg/m was administered orally twice daily until day 15, followed by a 7-day drug holiday period. The primary end point was 6-month progression-free survival (PFS) rate.
In total, 17 patients were enrolled in this study. The 6-month PFS rate was 64.7% [95% confidence interval (CI)=41.99-87.43], median PFS was 10.1 months (95%CI=4.11-17.28), and median overall survival was 21.8 months (95%CI=9.79-37.91). The response rate was 23.5% (95%CI=6.81-49.90%). Grade ≥3 adverse events were observed in 10% of patients, and included leukopenia [3 (17.6%)], neutropenia [5 (29.4%)], anorexia [2 (11.8%)], diarrhea [2 (11.8%)], and hypertension [3 (17.6%)]. No treatment-related deaths or febrile neutropenia were observed.
The SIRB regimen might be a promising second-line treatment option for patients with oxaliplatin and cetuximab-refractory KRAS wild-type mCRC in terms of efficacy and safety.
背景/目的：血管生成抑制剂在抗表皮生长因子受体抗体药物治疗方案进展后作为二线治疗用于 RAS 野生型转移性结直肠癌（mCRC）的疗效尚未得到充分研究。因此，我们进行了一项 II 期研究，以验证 S-1 和伊立替康联合贝伐珠单抗（SIRB 方案）作为二线治疗方案对奥沙利铂和西妥昔单抗耐药的 KRAS 野生型 mCRC 患者的疗效和安全性。
本研究纳入了先前接受过含奥沙利铂和西妥昔单抗方案治疗的 mCRC 患者。患者接受贝伐珠单抗 7.5 mg/kg 和伊立替康 150 mg/m2 静脉输注，第 1 天，而 S-1 80 mg/m2 每天口服 2 次，持续 15 天，随后停药 7 天。主要终点为 6 个月无进展生存期（PFS）率。
本研究共纳入 17 例患者。6 个月 PFS 率为 64.7%（95%CI=41.99-87.43），中位 PFS 为 10.1 个月（95%CI=4.11-17.28），中位总生存期为 21.8 个月（95%CI=9.79-37.91）。客观缓解率为 23.5%（95%CI=6.81-49.90%）。10%的患者出现≥3 级不良事件，包括白细胞减少症[3（17.6%）]、中性粒细胞减少症[5（29.4%）]、厌食症[2（11.8%）]、腹泻[2（11.8%）]和高血压[3（17.6%）]。未观察到与治疗相关的死亡或发热性中性粒细胞减少症。
SIRB 方案可能是奥沙利铂和西妥昔单抗耐药的 KRAS 野生型 mCRC 患者一种有前途的二线治疗选择，在疗效和安全性方面均具有优势。
