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

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

Friedemann Schad  1   2 , Anja Thronicke  1 , Megan L Steele  3 , Antje Merkle  1   2 , Burkhard Matthes  1   2 , Christian Grah  1   4 , Harald Matthes  1   5
Affiliations
Observational Study

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

Friedemann Schad et al. PLoS One. .

Erratum in

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.

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Conflict of interest statement

Dr. Schad reports grants from Helixor Heilmittel GmbH, grants from Abnoba GmbH, grants from Iscador AG, outside the submitted work. Dr. Grah reports grants from Iscador AG, outside the submitted work. Grants from Helixor Heilmittel GmbH include travel costs and honoraria for speaking. There are no other relationships/conditions/circumstances that present a potential conflict of interest. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No payment was received for any other aspects of the submitted work. The other authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of the study population.
NO, network oncology; CTx, Chemotherapy; VA, Viscum album L., mistletoe.
Fig 2
Fig 2. One-year survival.
Kaplan–Meier survival curves displaying one-year survival in stage IV NSCLC patients treated either with CTx alone or with combinational CTx plus VA, n = 158; CTx, chemotherapy; VA, Viscum album L.
Fig 3
Fig 3. Three-year survival.
Kaplan–Meier survival curves displaying 3-year survival in stage IV NSCLC patients treated either with CTx alone or with combinational CTx plus VA, n = 158; CTx, chemotherapy; VA, Viscum album L.
Fig 4
Fig 4. Kaplan-Meier curves of progression-free survival (PFS) for the both treatment cohorts CTx and CTx + VA.
Median PFS CTx: 4.4 months (95%CI: 2.7–5.9) vs. median PFS CTx+VA: 6.7 months (95%CI: 4.0–9.0), χ2 = 3.4, p = 0.06.
See this image and copyright information in PMC

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