高低累积顺铂剂量同步放化疗治疗鼻咽癌的疗效分析

doi:10.6040/j.issn.1673-3770.0.2025.123

摘要/Abstract

摘要： 目的通过Meta分析量化比较累积顺铂剂量(cumulative cisplatin dose, CCD)≤200 mg/m²与>200 mg/m²的生存获益及毒性差异,为个体化治疗提供循证依据。方法系统检索PubMed、Embase、Web of Science、Cochrane Library、中国生物医学数据库,检索时限为建库至2025年2月。观察指标包括5年总生存期［5-OS(overall survival)］、5年无进展生存期［5-PFS(progression free survival)］、5年无远处转移生存期［5-DMFS(distant metastasis free survival)］和毒性反应(adverse events, AEs)。使用RevMan 5.4软件进行Meta分析,根据I²值对纳入的文献进行异质性检验,并采用漏斗图筛选潜在的发表偏倚。结果共纳入9项队列研究,收集7 418例鼻咽癌患者相关数据,其中CCD≤200 mg/m²队列5 899例,CCD>200 mg/m²队列1 519例。与CCD>200 mg/m²相比,CCD≤200 mg/m²的治疗在5-OS(RR=0.98,95%CI:0.96~1.00)、5-PFS(RR=0.96,95%CI:0.91~1.01)及5-DMFS(RR=0.97,95%CI:0.93~1.01)方面差异无统计学意义。进一步对5-OS及5-DMFS进行的亚组分析也同样支持这一结果。在AEs方面,急性毒性中,CCD≤200 mg/m²队列1~4级白细胞减少症(RR=0.91,95%CI:0.86~0.97)、1~4级ALT升高(RR=0.69,95%CI:0.58~0.82)、肌酐升高(1~4级:RR=0.73,95%CI:0.60~0.88;3~4级:RR=0.20,95%CI:0.04~0.89)发生率均低于CCD>200 mg/m²队列;晚期毒性中,1~4级听力损伤(RR=0.81,95%CI:0.70~0.94)和皮肤纤维化(1~4级:RR=0.77,95%CI:0.64~0.92;3~4级:RR=0.43,95%CI:0.21~0.89)在CCD≤200 mg/m²队列也表现出较低的发生趋势。其他各级别AEs如3~4级白细胞减少症、3~4级ALT升高、3~4级听力损伤及贫血、血小板减少症、嗜中性白血球减少症、AST升高、口干、牙关紧闭、颅神经病变等毒性在队列间的差异均无统计学意义。结论在鼻咽癌同步放化疗治疗中,CCD≤200 mg/m²在疗效方面可能与CCD>200 mg/m²相似,但AEs的发生风险有所降低。

关键词: 鼻咽癌, 顺铂, 化放疗, 疗效比较研究, Meta分析

Abstract: Objective The objective of this study is to conduct a quantitative comparison of the survival efficacy and adverse reactions between the cumulative cisplatin dose(CCD)≤200 mg/m² cohort and the CCD>200 mg/m² cohort through meta-analysis, providing an evidence-based rationale for individualised treatment. Methods A systematic search was conducted across PubMed, Embase, Web of Science, Cochrane Library and Chinese Biomedical Literature Database up to February 2025. The observational indexes included 5-year overall survival(5-OS), 5-year progression free survival(5-PFS), 5-year distant metastasis free survival(5-DMFS)and adverse events(AEs). RevMan 5.4 software was utilized to perform the meta-analysis. The heterogeneity among the included studies was assessed using I² values. Furthermore, funnel plots were used to evaluate potential publication bias. Results Nine cohort studies were included. Data covering 7,418 patients diagnosed with nasopharyngeal cancer were collected, includeding 5,899 cases in the CCD≤200 mg/m² cohort and 1,519 cases in the CCD >200 mg/m² cohort. In comparison with the cohort of CCD >200 mg/m², the CCD≤200 mg/m² cohort did not exhibit a statistically significant reduction in 5-OS(RR=0.98,95%CI:0.96-1.00), 5-PFS(RR=0.96,95%CI:0.91-1.01)and 5-DMFS(RR=0.97,95%CI:0.93-1.01). Further subgroup analyses of 5-OS and 5-DMFS yielded consistent results. In relation to AEs, the CCD≤200 mg/m² cohort demonstrated a conspicuously diminished occurrence of acute toxic reactions compared to the CCD >200 mg/m² cohort. This was observed in grade 1-4 leukopenia(RR=0.91,95%CI:0.86-0.97),grade 1-4 ALT elevation(RR=0.69,95%CI:0.58-0.82)and any grade of creatinine elevation(grade 1-4: RR=0.73,95%CI:0.60-0.88; grade 3-4: RR=0.20,95%CI:0.04-0.89). With regard to late toxicities, both grade 1-4 hearing impairment(RR=0.81,95%CI:0.70-0.94)and any grade of dermal fibrosis(grade 1-4:RR=0.77,95%CI:0.64-0.92; grade 3-4: RR=0.43,95%CI:0.21-0.89)exhibited a substantial reduction within the CCD≤200 mg/m² cohort. However, no statistically significant differences were found between the two cohorts in other AEs, including grade 3-4 leukopenia, grade 3-4 ALT increase, grade 3-4 hearing impairment and any grade of anemia, thrombocytopenia, neutrophilic leukopenia, AST increase, dry mouth, clenching of teeth or cranial neuropathy. Conclusion This study indicates that in the treatment of nasopharyngeal carcinoma with concurrent chemoradiotherapy(CCRT), CCD≤200 mg/m² may achieve therapeutic efficacy comparable to that of CCD>200 mg/m², and may potentially reduce the risk of AEs.

Key words: Nasopharyngeal Carcinoma, Cisplatin, Chemoradiotherapy, Comparative Effectiveness Research, Meta-Analysis

中图分类号:

R766.3

孙春晓,王文晴,岳田,刘济生. 高低累积顺铂剂量同步放化疗治疗鼻咽癌的疗效分析[J]. 山东大学耳鼻喉眼学报, 2025, 39(4): 31-41.

SUN Chunxiao, WANG Wenqing, YUE Tian, LIU Jisheng. Efficacy analysis of concurrent chemoradiotherapy with high and low cumulative cisplatin doses in the treatment of nasopharyngeal carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(4): 31-41.

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