Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
Int J Clin Oncol. 2022 Aug;27(8):1300-1308. doi: 10.1007/s10147-022-02179-9. Epub 2022 May 30.
Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients.
Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933).
57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%).
Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.
regorafenib 显著改善了先前治疗的转移性结直肠癌患者的总生存期。然而，手足皮肤反应（HFSR）、疲劳和肝功能障碍等各种毒性限制了regorafenib 的使用。这些毒性在治疗开始后不久就会出现。ReDOS 研究表明，regorafenib 起始剂量较低的每周剂量递增治疗是有效的；然而，其在亚洲人群中的有效性尚不清楚。我们进行了一项 II 期研究，以评估regorafenib 剂量递增治疗对日本患者的安全性和生存获益。
纳入具有足够器官功能、先前接受过两线以上化疗的患者。regorafenib 起始剂量为 80mg/天，如果没有严重的药物相关毒性，则在第 2 周和第 3 周分别递增至 120mg/天和 160mg/天。主要终点是无进展生存期（PFS）。每 8 周进行一次影像学评估肿瘤反应和进展。本研究在大学医院医疗信息网络（UMIN#UMIN000028933）注册。
共纳入 57 例患者，所有患者均起始接受 80mg/天的 regorafenib 治疗。其中 32 例（56.1%）随后递增至 120mg/天，19 例（33.3%）递增至 160mg/天。仅 8 例（14.0%）因不良事件停止治疗。中位 PFS 为 1.9 个月。中位总生存期为 8.9 个月，客观缓解率为 0%，疾病控制率为 31.6%。大于 3 级的最常见不良事件是高血压（19.3%），其次是 HFSR（14.0%）。
regorafenib 剂量递增治疗与标准 regorafenib 治疗的 PFS 相似，具有良好的耐受性。
