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含冬凌草甲素的冬凌草制剂联合化疗治疗Ⅳ期非小细胞肺癌患者的真实世界多中心观察性分析

Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis.

机构信息

Research Institute Havelhöhe, Hospital Havelhöhe, Berlin, Germany.

Interdisciplinary Oncology and Palliative Care, Hospital Havelhöhe, Berlin, Germany.

出版信息

PLoS One. 2018 Aug 27;13(8):e0203058. doi: 10.1371/journal.pone.0203058. eCollection 2018.

Abstract

BACKGROUND

Stage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients.

METHODS

The observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed.

RESULTS

The median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0-40.0) and was 8.0 months (95%CI: 7.0-11.0) in the CTx only group (χ2 = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26-0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%).

CONCLUSION

Our findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowldedge of add-on VA's clinical impact, however, results should be interpreted with caution in light of the study's observational character.

摘要

背景

IV 期非小细胞肺癌(NSCLC)的五年生存率约为 1%。已证实,服用鹿花毒素 L.(VA)提取物可减少化疗(CTx)相关不良反应、降低 CTx 剂量减少并改善多种癌症患者的生活质量。最近的数据表明,添加鹿花毒素 L.(VA,欧洲槲寄生)治疗对癌症患者的生存有有益影响。本研究的目的是评估 IV 期 NSCLC 患者在 CTx 基础上加用 VA 的疗效。

方法

本观察性研究使用德国肿瘤医院、医师和门诊中心联合临床注册网络肿瘤学临床登记处的数据进行。入组患者诊断为 IV 期 NSCLC,确诊后至少生存四周,接受化疗治疗。不包括 EGFR 突变患者以及接受酪氨酸激酶抑制剂或免疫检查点抑制剂的患者。比较 CTx 治疗患者和 CTx 加 VA 治疗患者的总生存率,并比较对危险度的影响。为了确定与生存相关的因素并解决潜在的偏倚来源,使用 Cox 比例风险模型进行了多变量分析。

结果

该人群的中位年龄为 64.1 岁,男性占 55.7%。最高比例的患者患有腺癌(72.2%),大多数患者为现吸烟者或既往吸烟者(70.9%)。158 例 IV 期 NSCLC 患者中,108 例仅接受 CTx 治疗,50 例额外接受 VA 治疗。CTx 加 VA 组的中位总生存期为 17.0 个月(95%CI:11.0-40.0),仅接受 CTx 组为 8.0 个月(95%CI:7.0-11.0)(χ2 = 7.2,p =.007)。VA 组的总生存期显著延长(HR 0.44,95%CI:0.26-0.74,p =.002)。与仅接受 CTx 相比,CTx 加 VA 治疗的 1 年和 3 年总生存率更高(1y:60.2% vs. 35.5%;3y:25.7% vs. 14.2%)。

结论

我们的研究结果表明,在接受标准 CTx 治疗的 IV 期 NSCLC 患者中,同时使用 VA 与生存呈正相关。这些发现补充了 VA 附加治疗的临床影响的现有知识,但鉴于研究的观察性质,结果应谨慎解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f8/6110500/ce102efce238/pone.0203058.g001.jpg

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