Mistletoe therapy for lung cancer

• Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L. – a real‑world data 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 multicentre analysis
• Effects of additive mistletoe therapy on quality of life and chemotherapy-related side effects in patients with advanced non-small cell lung cancer – a randomised phase II study
• Effects of complementary mistletoe therapy on the quality of life of patients with breast, ovarian and non-small cell lung cancer – a prospective randomised controlled clinical trial
• Efficacy and safety of Viscum album extract to treat malignant pleural effusion in patients with lung cancer
• Viscum pleurodesis is similarly effective to talc pleurodesis and appears to have fewer side effects

The results in the chapter health services research are also to be considered in this context.

Schad et al. 2023 [330]

Patients and methods

This monocentric real-world data study included patients with histologically confirmed primary lung cancer who were investigated and treated at the German Cancer Society-certified lung cancer centre at the hospital Gemeinschaftskrankenhaus Havelhöhe in Berlin. For this purpose, evaluable data sets on self-reported quality of life had to be available at least at the time of initial diagnosis (T0) and 12 months later (T1). The data on tumour stage (UICC), performed surgeries and radiotherapy, treatment regimens and self-reported quality of life were retrieved from the Network Oncology Registry. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Health-Related Quality of Life Questionaire scale (EORTC QLQ-C30). An adjusted multivariate linear regression analysis was performed to analyse the factors associated with changes in quality of life after 12 months.

Results

A total of 112 patients with primary lung cancer of all stages, with 92% suffering from non-small cell lung cancer and a mean age of 70 years, were divided into 4 groups:

• 27 patients received neither radiotherapy nor mistletoe therapy and served as a reference group
• 29 patients received mistletoe therapy without radiotherapy
• 32 patients were treated with radiotherapy and did not receive mistletoe therapy
• 24 patients were treated with radiotherapy and mistletoe therapy

They answered the questionnaires at initial diagnosis and 12 months later. The quality of life assessment after 12 months showed a significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received radiotherapy and mistletoe therapy. Significant improvements of 15 to 21 points were also observed for role function (p = 0.03) as well as physical (p = 0.02), cognitive (p = 0.04) and social function (p = 0.04) in patients who received mistletoe therapy without radiotherapy.

Conclusion

Additional mistletoe therapy had a positive effect on the quality of life of lung cancer patients. A significant reduction in pain and nausea/vomiting was observed, particularly in patients undergoing radiotherapy.

Schad et al. 2018 [100]

Patients and methods

The data for this non-randomised multicentre observational study in 158 patients with histologically confirmed stage IV non-small cell lung cancer (NSCLC) were obtained from the clinical register of the Network Oncology (NO database).

To determine the influence of mistletoe therapy on survival time, data from two patient groups were included. One group of 108 patients received only chemotherapy and the other group of 50 patients received a combination of chemotherapy and mistletoe therapy. Only patients who were still alive for at least 28 days after diagnosis were analysed. The average age was about 64 years; there were no statistically significant differences between the two groups.

First-line chemotherapy consisted of platinum compounds (73.4%), often in combination with gemcitabine, pemetrexed, vinorelbine or etoposide. Patients receiving additional mistletoe therapy (with abonbaVISCUM, Helixor, Iscador) mostly received s.c. administration, sometimes in combination with infusions (off-label).

Results

Median overall survival was 17 months in the group with additional mistletoe therapy compared to 8 months in the group receiving chemotherapy alone. The difference was statistically significant (p = 0.007). The one-year survival rate was 35.5 percent in the chemotherapy group compared to 60.2 percent in the group with additional mistletoe therapy and the three-year survival rate was 14.2 percent compared to 25.7 percent.

The adjusted multivariate stratified Cox proportional hazard analysis showed that concomitant mistletoe therapy in stage IV NSCLC patients significantly reduced the risk of death by 56 percent compared to chemotherapy alone (adjusted hazard ratio: 0.44, 95% CI = 0.26-0.74, p = 0.002). In addition, an extension of mistletoe therapy at ≥ 16 weeks significantly reduced the risk of death (p = 0.007).

Conclusion

The results of this real-world data study suggest that patients with stage IV NSCLC who received combined chemotherapy and mistletoe therapy have a significantly longer survival than patients who received chemotherapy alone. These real-world study results should be complemented by prospective randomized studies.

Bar-Sela et al. 2013 [76]

Patients and methods

In this randomised phase II study, patients with unresectable non-small cell lung cancer (NSCLC) under therapy with gemcitabine/carboplatin or premetrexed/carboplatin were included. They were divided into two groups by 1:1 randomisation. One group of 33 patients additionally received the mistletoe extract Iscador Qu, the other group of 39 patients did not receive any concomitant therapy. The aim of this study was to examine whether mistletoe therapy can reduce the side effects of chemotherapy and improve quality of life.

Results

The patients in the mistletoe therapy group showed significantly fewer chemotherapy-related side effects, with the result that significantly more chemotherapy cycles could be given. The progression-free period was 4.8 months in the control group and 6 months in the mistletoe therapy group; overall survival was 13.3 (control group) and 15.9 months (verum group). Due to the small number of cases, however, these differences were not significant.

With the exception of the parameter "pain in shoulder", the quality of life measurements always showed an advantage for the patients in the mistletoe therapy group.

There was only one side effect of grade II in the mistletoe therapy group resulting in an oversized local reaction at the injection site. Thus the therapy could be classified as safe.

Conclusion

The additive mistletoe therapy parallel to chemotherapy can reduce chemotherapy-related side effects.in late stage NSCLC patients These results should be verified in larger phase III studies.
 

Piao et al. 2004 [31]

The results of this study for patients with lung cancer are discussed in the section on breast cancer.

Lee et al. 2019 [290]

Patients and methods

In this retrospective study, 52 patients with lung cancer and malignant pleural effusions underwent pleurodesis with the mistletoe preparation Helixor M instead of talc between 2008 and 2015. The primary study objective was defined as the recurrence of pleural effusion one month after the last pleurodesis procedure. For this purpose, 100 mg of mistletoe extract was instilled via a pleural catheter on day 1. If the procedure was ineffective the first time, it was repeated every other day up to five times and the dose of mistletoe extract was increased by 100 mg each time.

Results

The median age of patients with lung cancer was 63 years and 77 percent were male. The most common histopathologic diagnosis was adenocarcinoma in 36 (69%) patients, followed by squamous cell carcinoma in 7 (13%), non-small cell lung cancer in 5 (10%) and small cell lung cancer in 4 (8%) patients. Approximately 85% of pleural effusions were classified as malignant by cytogenetic examination.

Forty-two (81%) of the 52 patients could be evaluated for recurrent malignant pleural effusion. The 1-month recurrence rate was 48% (20/42). Of the 20 patients who developed a recurrent malignant pleural effusion, 6 needed therapeutic pleural puncture. Thirteen (25%) patients had treatment-related pain that required medication. Eight (15%) patients showed temperatures greater than 38 °C.

Patients received a median of three instillations of Helixor M for pleurodesis and six patients received five instillations. Of these six patients, two were resistent to therapy, i.e. they did not respond to maximal treatment.

The success rate of pleurodesis with Helixor M in the treatment of recurrent malignant pleural effusion was 52 percent. Although the data did not show superior results to talc pleurodesis, the results of pleurodesis with Helixor were comparable to those of pleurodesis with other agents such as bleomycin or tetracycline.

Conclusion

The results indicate that pleurodesis with the mistletoe preparation Helixor can be considered an effective and tolerable alternative for the treatment of malignant pleural effusions in patients with lung cancer.

Chang et al. 2020 [314]

Patients and methods

A retrospective data analysis of 56 patients with malignant pleural effusion who received either chemical pleurodesis with talc (30 patients) or the mistletoe extract AbnobaVISCUM Fraxini (26 patients) after thoracostomy was performed to analyse their clinical course and response after pleurodesis.

Results

Body temperature, leukocyte count and CRP levels were increased after talc pleurodesis. Thus, body temperature increased from 36.6 ± 0.3 to 37.7 ± 0.7 °C, leukocyte count increased from 7,100 ± 2,930 to 12,046 ± 6,210 cells/mm³, and CRP increased from 9.62 ± 8.85 to 16.09 ± 9.04 mg/dl. The degree of pain measured by numeric rating scale (NRS) increased from 1.4 ± 1.1 to 2.7 ± 1.3. After talc pleurodesis, it took 4.6 ± 4.2 days to remove the chest tube. The total drainage volume was 476 ± 601 ml.

Viscum pleurodesis showed a similar pattern to talc pleurodesis. For example, body temperature increased from 36.7 ± 0.4 to 37.7 ± 0.6 °C, leukocyte count increased from 8,450 ± 2,680 to 14,110 ± 5,203 cells/mm3, and CRP increased from 4.75 ± 4.35 to 12.3 ± 6.6 mg/dl. Pain level increased from 2.0 ± 1.5 to 2.5 ± 1.7, and it took 5.2 ± 4.2 days to remove the chest tube. The total drainage volume was 756 ± 1048 ml.

Regarding the final response rate after pleurodesis, 36.7% in the talc group and 60.0% in the Viscum group showed a complete response, 56.7% in the talc group and 36.0% in the Viscum group showed a partial response and 6.7% in the talc group and 4.0% in the Viscum group did not respond to pleurodesis.

An acute respiratory distress syndrome and pneumonitis were noted in the talc group and an acute respiratory distress syndrome in the Viscum group. Deaths due to pleurodesis did not occur. However, pleurodesis with talc is associated with milder side effects such as pain and fever and more severe complications such as lung injury, and although the intensity of pain experienced by patients and the degree of change in fever-related measurements were similar in the two groups, patients in the Viscum group perceived the pain and fever as less impairung than patients in the talc group, suggesting that they generally tolerated the procedure better.

Conclusion

Viscum pleurodesis showed comparable treatment results to talc pleurodesis, while adverse effects such as chest pain and fever were found to be less in the Viscum group.