Marucci Marena A, Lechner Doreen W, Tafuto Barbara A
Department of Health Informatics, School of Health Professions, Rutgers, The State University of New Jersey, 65 Bergen Street, Newark, NJ 07107, USA.
Gastrointest Tract. 2024;2(1). doi: 10.54844/git.2023.482. Epub 2024 Mar 12.
Gastrointestinal stromal tumors (GIST) are a rare cancer where tumors grow along the gastrointestinal tract. While treatment options aim towards surgical resection, some patients present with advanced metastatic and/or nonresectable diseases. The tyrosine kinase inhibitor imatinib mesylate is approved for this indication. However, dose escalation from 400 to 600 mg/d or 800 mg/d is allowed. The present study systematically evaluates the safety outcomes, particularly the incidence of grade ⩾ 3 adverse events (AEs) with low dose compared with high dose imatinib in these patients.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines were utilized to identify relevant studies through the PubMed, Cochrane Library, and Ovid databases and included randomized and non-randomized clinical trials comparing a low dose intervention of imatinib 400 mg/d with a high dose comparator of 600 or 800 mg/d in patients with histologically confirmed advanced metastatic and/or nonresectable GIST. Four studies were reviewed regarding study summaries and patient characteristics, patient demographics, and risk of bias, with a main emphasis on the evaluation of both efficacy outcomes and safety outcomes.
Three of the four studies did not provide significant differences in response outcomes; however, all four studies reported a higher incidence of grade ⩾ 3 AEs in the high dose imatinib groups. Individual study reports of more high dose patients experiencing a grade ⩾ 3 event ranged from 0.6% to 19.8%, while combined low and high dose patient arms revealed a 17.1% difference favoring a high dose patient event. A sub-analysis of the three most frequently occurring categories, blood and lymphatic system disorders, gastrointestinal disorders, and general disorders and administration site conditions each revealed more high dose patients experiencing said category events compared to those low dose counterparts.
Low dose imatinib provides clinically meaningful response and demonstrated better tolerability with less frequently reported reactions. This evidence supports further research into the maintenance of 400 mg/d for this patient population compared to a dose escalation.
胃肠道间质瘤（GIST）是一种罕见的癌症，肿瘤沿胃肠道生长。虽然治疗方案旨在手术切除，但一些患者表现为晚期转移性和/或不可切除疾病。酪氨酸激酶抑制剂甲磺酸伊马替尼已获批准用于此适应症。然而，允许将剂量从400mg/天增加到600mg/天或800mg/天。本研究系统地评估了这些患者中低剂量与高剂量伊马替尼相比的安全性结果，特别是≥3级不良事件（AE）的发生率。
采用《系统评价和Meta分析的首选报告项目2020》指南，通过PubMed、Cochrane图书馆和Ovid数据库识别相关研究，纳入比较400mg/天伊马替尼低剂量干预与600或800mg/天高剂量对照的随机和非随机临床试验，这些患者组织学确诊为晚期转移性和/或不可切除GIST。对四项研究的研究总结、患者特征、患者人口统计学和偏倚风险进行了审查，主要侧重于疗效结果和安全性结果的评估。
四项研究中有三项在反应结果上未提供显著差异；然而，所有四项研究均报告高剂量伊马替尼组中≥3级AE发生率更高。个别研究报告显示，更多高剂量患者发生≥3级事件的比例在0.6%至19.8%之间，而低剂量和高剂量患者组合并显示，高剂量患者事件发生率有17.1%的差异。对三个最常见类别（血液和淋巴系统疾病、胃肠道疾病以及全身疾病和给药部位状况）的亚分析显示，与低剂量患者相比，每个类别中发生所述事件的高剂量患者更多。
低剂量伊马替尼提供了具有临床意义的反应，并显示出更好的耐受性，不良反应报告较少。这一证据支持进一步研究该患者群体维持400mg/天的剂量与增加剂量相比的情况。
