瑞戈非尼在晚期胃肠间质瘤治疗中的优化 策略：从标准方案到个体化治疗

Optimization Strategies of Regorafenib in Advanced Gastrointestinal Stromal Tumors: From Standard Regimen to Personalized Treatment

摘要: 胃肠间质瘤(gastrointestinal stromal tumor, GIST)是胃肠道最常见的间叶源性肿瘤。伊马替尼与舒尼替尼分别作为一、二线标准治疗，显著改善了晚期GIST患者的生存预后，但二者治疗失败后患者的治疗选择有限。瑞戈非尼作为多靶点酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)，已被证实为晚期GIST的标准三线治疗药物。其标准给药方案(160 mg/天，用药3周/停药1周)虽能显著延长无进展生存期(progression-free survival, PFS)，但不良事件发生率较高，导致多数患者需剂量调整或治疗中断，影响治疗持续性与临床获益。为优化瑞戈非尼的治疗效果、改善患者耐受性，近年来临床逐步探索了连续给药、剂量递增及个体化治疗等优化策略。本文系统检索国内外相关临床研究、真实世界数据及药理学研究文献，梳理上述优化策略的药理学基础、临床应用证据及实施要点，深入分析各策略的优势与局限性，以期为晚期GIST患者的临床精细化用药提供参考依据。

Abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Imatinib and sunitinib, as standard first-line and second-line therapies respectively, have significantly improved the survival prognosis of patients with advanced GIST. However, treatment options are limited after failure of both agents. Regorafenib, a multi-target tyrosine kinase inhibitor (TKI), has been established as the standard third-line treatment for advanced GIST. Although the standard dosing regimen (160 mg daily, 3 weeks on/1 week off) significantly prolongs progression-free survival (PFS), it is associated with a high incidence of adverse events, leading to dose modifications or treatment interruptions in the majority of patients, thereby compromising treatment continuity and clinical benefit. To optimize the therapeutic effect and improve tolerability of regorafenib, various optimization strategies including continuous dosing, dose escalation, and personalized treatment have been progressively explored in clinical practice. This review systematically examines relevant clinical studies, real-world data, and pharmacological research literature to summarize the pharmacological basis, clinical evidence, and implementation points of these optimization strategies. The advantages and limitations of each strategy are analyzed in depth, aiming to provide a reference for precision medication in patients with advanced GIST.