Thronicke Anja, Steele Megan L, Grah Christian, Matthes Burkhard, Schad Friedemann
Forschungsinstitut Havelhöhe gGmbH, Kladower Damm 221, 14089, Berlin, Germany.
Institute of Health and Biomedical Innovation, School of Public Health and Social Work, Queensland University of Technology, Park Road, Brisbane, VIC, 4059, Australia.
BMC Complement Altern Med. 2017 Dec 13;17(1):534. doi: 10.1186/s12906-017-2045-0.
Despite improvement of tumour response rates in patients with progressive and metastatic cancer, immune checkpoint inhibitors (ICM) induce toxicities in cancer patients. Viscum album L. (VA, mistletoe) extracts are applied as add-on cancer therapy especially in German speaking countries and within integrative and anthroposophical concepts with the goal to improve quality of life. The primary objective of this pilot observational cohort study was to determine the rate of adverse events (AE) related to ICM therapy with and without VA in patients with advanced or metastatic cancer in a certified Cancer Center.
ICM or combined ICM/VA therapies were applied in patients with progressive or metastatic cancer. AE rates of both therapy groups were compared.
A total of sixteen cancer patients were treated with ICM: nivolumab (75%), ipilimumab (19%) or pembrolizumab (6%). The median age of the study population was 64 years (IQR 57.8; 69.3); 44% were male. Of the sixteen patients receiving ICM, nine patients received additional VA (56%; ICM/VA group) and seven did not (44%; ICM group). No statistically significant differences were seen between groups with respect to AE-rates (67% ICM/VA versus 71% ICM). Adjusted multivariate regression analysis revealed that concomitant application of VA did not alter the AE rate in ICM treated patients. 85% of AEs were expected ICM reactions. No AEs of grade 3 or greater were documented for the total study cohort.
This is the first study evaluating the clinical safety profile of ICM in combination with VA in patients with advanced or metastatic cancer. The overall AE rate of the study cohort is comparable to AE rates of ICM treatment in the literature. Our data indicate a first impression that concomitant VA application may not alter ICM-induced AE rates. However, the nature of this study does not allow excluding possible immunological interactions between ICM and VA. Further prospective trials in larger study cohorts should focus on the assessment of safety aspects, clinical efficacy and health related quality of life in patients with combined ICM/VA therapy.
DRKS00013335 , retrospectively registered (November 27th, 2017) at the German Clinical Trials Register ( www.drks.de ).
尽管进展期和转移性癌症患者的肿瘤缓解率有所提高，但免疫检查点抑制剂（ICM）会在癌症患者中引发毒性反应。欧洲白槲寄生（VA，槲寄生）提取物作为辅助癌症治疗手段被应用，尤其在德语国家以及综合医学和人智学理念中，目的是提高生活质量。这项初步观察性队列研究的主要目的是确定在一家认证癌症中心，晚期或转移性癌症患者接受ICM治疗时，无论有无VA辅助，与之相关的不良事件（AE）发生率。
对进展期或转移性癌症患者应用ICM或联合ICM/VA疗法。比较两个治疗组的AE发生率。
共有16例癌症患者接受了ICM治疗：纳武单抗（75%）、伊匹单抗（19%）或派姆单抗（6%）。研究人群的中位年龄为64岁（四分位间距57.8；69.3）；44%为男性。在接受ICM治疗的16例患者中，9例患者额外接受了VA治疗（56%；ICM/VA组），7例未接受（44%；ICM组）。两组在AE发生率方面未见统计学显著差异（ICM/VA组为67%，ICM组为71%）。校正后的多变量回归分析显示，联合应用VA并未改变ICM治疗患者的AE发生率。85%的AE为预期的ICM反应。整个研究队列未记录到3级或更高级别的AE。
这是第一项评估ICM联合VA治疗晚期或转移性癌症患者临床安全性的研究。该研究队列的总体AE发生率与文献中ICM治疗的AE发生率相当。我们的数据初步显示，联合应用VA可能不会改变ICM引发的AE发生率。然而，本研究的性质不允许排除ICM与VA之间可能存在的免疫相互作用。在更大规模研究队列中开展的进一步前瞻性试验应聚焦于联合ICM/VA治疗患者的安全性评估、临床疗效及健康相关生活质量评估。
DRKS00013335，于2017年11月27日在德国临床试验注册中心（www.drks.de）进行回顾性注册。
