Fan Shaoqing, Zhao Zeming, Wang Haiqian, Wang Handong, Niu Wenbo
Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Front Oncol. 2025 Apr 7;15:1567732. doi: 10.3389/fonc.2025.1567732. eCollection 2025.
The global burden of colorectal cancer (CRC) continues to rise, with elderly populations disproportionately affected. Despite oxaliplatin's established role in first-line metastatic CRC (mCRC) therapy, its clinical utility in older adults remains debated due to concerns over efficacy, toxicity, and survival outcomes. This meta-analysis evaluates the therapeutic benefits and risks of oxaliplatin-based regimens in elderly patients with mCRC, with emphasis on tumor response, survival endpoints, and treatment-related toxicities.
We systematically reviewed PubMed, Web of Science, Cochrane Library, and Chinese databases (CNKI, Wan Fang) through November 2024 for randomized controlled trials (RCTs) comparing oxaliplatin-based chemotherapy to non-oxaliplatin regimens in patients aged ≥65 with mCRC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR), and grade 3-4 adverse events. Data were pooled using random- or fixed-effects models in STATA 14.0 based on heterogeneity (I² statistic). Subgroup analyses explored heterogeneity sources, including chemotherapy combinations (e.g., bevacizumab, panitumumab).
Seven RCTs (1,839 patients) met inclusion criteria. Oxaliplatin significantly improved tumor response rates versus control regimens: ORR (OR 2.18, 95% CI 1.75-2.72; <0.001), CR (OR 2.57, 1.11-5.97; =0.028), and PR (OR 1.69, 1.28-2.22; <0.001). No significant survival benefit was observed for OS (HR 0.97, 0.86-1.08; =0.58) or PFS (HR 0.90, 0.79-1.01; =0.07), though trends favored oxaliplatin. Grade 3-4 neutropenia (RR 1.84, 1.32-2.57), diarrhea (RR 2.01, 1.45-2.78), and sensory neuropathy (RR 3.12, 1.98-4.91) were more frequent with oxaliplatin. Subgroup analysis attributed DCR heterogeneity (I²=66%) to regimen differences, with reduced variability in bevacizumab/pantiumumab-combined subgroups.
This analysis demonstrates oxaliplatin's capacity to enhance tumor response in elderly mCRC patients, potentially alleviating symptoms and improving quality of life. However, the absence of significant survival gains underscores the complex interplay between tumor biology and therapeutic resistance. Mechanistically, chemotherapy-driven clonal selection may favor residual resistant subpopulations, as evidenced by liquid biopsy studies linking tumor evolution to disease progression. While toxicity profiles were manageable, the elevated risk of neurotoxicity and myelosuppression necessitates vigilant monitoring in this vulnerable cohort.
Oxaliplatin-based first-line therapy provides clinically meaningful tumor response improvements in elderly mCRC patients, though survival advantages remain elusive. Treatment decisions should balance response benefits against toxicity risks, prioritizing individualized strategies informed by geriatric assessments and molecular profiling. Future trials must integrate biomarker-driven approaches (e.g., ctDNA monitoring, RAS/RAF stratification) to optimize therapeutic precision in aging populations.
结直肠癌（CRC）的全球负担持续上升，老年人群受影响的比例尤其高。尽管奥沙利铂在一线转移性CRC（mCRC）治疗中已确立其作用，但其在老年人中的临床效用仍存在争议，原因是对疗效、毒性和生存结果存在担忧。本荟萃分析评估了基于奥沙利铂的治疗方案在老年mCRC患者中的治疗益处和风险，重点关注肿瘤反应、生存终点和治疗相关毒性。
我们系统检索了截至2024年11月的PubMed、科学网、Cochrane图书馆和中文数据库（中国知网、万方），以查找比较基于奥沙利铂的化疗与非奥沙利铂方案治疗≥65岁mCRC患者的随机对照试验（RCT）。结局指标包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、完全缓解（CR）、部分缓解（PR）、疾病控制率（DCR）和3-4级不良事件。根据异质性（I²统计量），在STATA 14.0中使用随机或固定效应模型汇总数据。亚组分析探讨了异质性来源，包括化疗联合用药（如贝伐单抗、帕尼单抗）。
七项RCT（1839例患者）符合纳入标准。与对照方案相比，奥沙利铂显著提高了肿瘤缓解率：ORR（OR 2.18，95%CI 1.75-2.72；P<0.001）、CR（OR 2.57，1.11-5.97；P=0.028）和PR（OR 1.69，1.28-2.22；P<0.001）。未观察到OS（HR 0.97，0.86-1.08；P=0.58）或PFS（HR 0.90，0.79-1.01；P=0.07）有显著生存获益，尽管趋势有利于奥沙利铂。奥沙利铂组3-4级中性粒细胞减少（RR 1.84，1.32-2.57）、腹泻（RR 2.01，1.45-2.78）和感觉神经病变（RR 3.12，1.98-4.91）更为常见。亚组分析将DCR异质性（I²=66%）归因于方案差异，在贝伐单抗/帕尼单抗联合亚组中变异性降低。
本分析表明奥沙利铂能够增强老年mCRC患者的肿瘤反应，可能缓解症状并改善生活质量。然而，未观察到显著的生存获益凸显了肿瘤生物学与治疗耐药性之间复杂的相互作用。从机制上讲，化疗驱动的克隆选择可能有利于残留的耐药亚群，液体活检研究将肿瘤演变与疾病进展联系起来就证明了这一点。虽然毒性特征是可控的，但神经毒性和骨髓抑制风险升高，因此需要对这一脆弱人群进行密切监测。
基于奥沙利铂的一线治疗可使老年mCRC患者的肿瘤反应在临床上有意义地改善，尽管生存优势仍不明显。治疗决策应在反应益处与毒性风险之间取得平衡，优先考虑基于老年评估和分子谱分析的个体化策略。未来的试验必须整合生物标志物驱动的方法（如循环肿瘤DNA监测、RAS/RAF分层），以优化老年人群的治疗精准度。
