Influence of mistletoe therapy on survival time and quality of life in patients with locally advanced or metastatic pancreatic cancer – a randomised clinical phase III study

Tröger et al. 2013, 2014 [81, 127]

These are two publications of a study which has been published under different aspects in several scientific journals.

Patients and methods

In this open-label, monocentre, group-sequential, randomised phase III trial in patients with locally advanced or metastatic pancreatic cancer the patients were monitored for a period of twelve months or until their death.

Half of the patients received best supportive care for acute treatment of cancer-related symptoms, but no antineoplastic therapy. The other half additionally injected the mistletoe extract Iscador Qu subcutaneously three times a week. Subsequently, both groups were compared with regard to overall survival and quality of life. Quality of life was assessed using the EORTC QLQ-C30 questionnaire.

The group sequential design involved a first interim analysis of overall survival and drug safety by an independent review board (Independent Data Monitoring Board, IDMC) after the inclusion of 220 patients. This board recommended an early termination of the study as the planned interim analysis of the data showed a prevalence of mistletoe therapy with regard to overall survival and agreed to the publication of the study results obtained so far.

Results

The baseline characteristics were statistically balanced in both study groups. The interim analysis showed a median survival time of 4.8 months in the mistletoe group compared to 2.7 months in the control group (hazard ratio (HR) = 0.49; p < 0.0001). In two following subgroup analyses, in which the patients were divided according to a prognosis index, the median survival time in the group with "good prognosis" was 6.6 months for the patients with mistletoe therapy and 3.2 months for the control group (HR = 0.43; p < 0.0001). In the group of patients with "poor prognosis" the corresponding survival times were 3.4 and 2.0 months respectively (HR = 0.55; p < 0.0031).

The parameters for quality of life were also mostly significantly different between the both groups. For example, EORTC QLQ-C30 showed a significant and clinically relevant advantage in the mistletoe group in 13 of its 15 dimensions. The significant improvement was also reflected in the reduced number and severity of cancer-related symptoms in the course of treatment. In particular, cancer-related pain was significantly lower, which was accompanied by a significant reduction in analgesics. In addition, nausea and vomiting as well as loss of energy and appetite were significantly less severe. Despite all expectations, the investigators even observed a slight weight gain in patients of the mistletoe group.

Mistletoe therapy was well tolerated and no serious side effects were recorded.

Conclusion

This study showed a significant and clinically relevant advantage in overall survival and a very significant improvement in the quality of life for patients undergoing mistletoe therapy. Mistletoe therapy thus represents a well tolerated treatment for patients with locally advanced or metastasised pancreatic adenocarcinoma.

Last update: 17. August 2020/AT

 

Integrative oncology including mistletoe therapy in palliative care of patients with advanced pancreatic cancer – a multicentre observational study

Axtner et al. 2016 [101]

Patients and methods

In this multicentre observational study the effect of an integrative oncological concept including mistletoe therapy in daily care was investigated on the overall survival of 240 patients with advanced pancreatic cancer (stage IV).

Survival time was analysed using multivariate Cox proportional hazard analysis with different parametric allocation functions. Patients who received chemotherapy alone were compared with those who received a combination of chemotherapy and mistletoe therapy or mistletoe therapy alone or no therapy at all. For classification into the mistletoe group a use of at least four weeks was required.
 

Results

Of the 240 patients, 124 were females and 116 males with a median age of 68 years. Of these, 221 (92.1%) received a complementary therapy as part of the integrative oncological therapy concept, and 177 (73.8%) of these received mistletoe therapy, which was used in addition to chemotherapy (mostly gemcitabine as monotherapy or in combination) in 154 patients (64.1%). Both therapies had positive effects on the patients' survival.

In a second analysis it was found that patients with combined chemo- and mistletoe therapy had a significantly longer survival time than patients who received chemotherapy alone (12.1 vs. 7.3 months). Patients who received only mistletoe therapy showed a longer survival time than those who received neither chemotherapy nor mistletoe therapy (5.4 vs. 2.5 months). The combination of both therapies therefore performed best.
 

Conclusion

The data show that an integrative oncological concept can be successfully applied in the daily care of patients with advanced pancreatic cancer. For example, the longest survival time was determined for patients who received both mistletoe therapy and chemotherapy.

 

Last update: August 17th, 2020/AT

Efficacy and safety of supportive mistletoe therapy in patients with pancreatic cancer of all stages of severity – a multicentre, controlled, retrospective epidemiological cohort study

Matthes et al. 2010 [45]

Patients and methods

This multicentre, controlled, epidemiological, retrospective cohort study, conducted according to GEP guidelines, included 396 patients from different centres in Germany and Switzerland with pancreatic cancer of all stages of severity (UICC stages I to IV). As part of a supportive therapy, Iscador was administered to 201 of these patients two to three times a week in addition to adjuvant chemotherapy (± radiotherapy) or complementary to oncological aftercare.

The 195 patients of the control group were treated with chemotherapy alone, in particular with gemcitabine (± radiotherapy), or received aftercare without further oncological medication.

The median treatment and follow-up period was about 15 months in the mistletoe group and about 10 months in the control group. The median duration of chemotherapy was about 7 months in the mistletoe group and about 5 months in the control group.

Efficacy was evaluated according to the frequency of side effects caused by chemotherapy (± radiotherapy) in the mistletoe group compared to the control group, as well as the persistence of disease-related symptoms, Karnofsky index, hospitalisation time and overall survival (OS). The number of patients with documented adverse events (ADR) caused by mistletoe therapy was also recorded.

Results

In the mistletoe group, significantly fewer side effects caused by chemo- and/or radiotherapy were observed than in the control group. Only 14 per cent of the mistletoe group developed these side effects, compared to almost 50 per cent in the control group. The adjusted relative risk to develop therapy-related side effects was thus significantly lower in the mistletoe group than in the control group (p = 0.003), (risk reduction of 54).

The patients in the mistletoe group showed fewer disease- and therapy-related symptoms after the first oncological treatment cycle. In particular, nausea, vomiting, loss of appetite, depression, fatigue, sleep disorders, and back pain occurred significantly less frequently than in the control group.

A remarkable study result was obtained for the estimated survival time. It was significantly longer in the mistletoe group than in the control group. The adjusted hazard ratio related to the mortality rate was 0.58 resulting in a reduction of the relative risk of death in the mistletoe group by approximately 42 percent compared to the control group.

The Karnofsky performance index also improved significantly in the mistletoe group. Performance increased from 74.1 to 79.1 percent in patients under mistletoe therapy after the first chemotherapy cycle. In contrast, the control group had a performance decrease from 80.3 to 74.7 percent. The average time of hospitalisation was also significantly shorter in the mistletoe group (40 days) compared to the control group (54 days).

To assess therapeutic safety, the adverse drug reactions caused by the mistletoe extract were evaluated. Only three patients (0.8%) from the mistletoe group reacted with mild, unspecific systemic side effects such as dizziness, exhaustion, depression, nausea or mild fever. In 45 patients (22.4%) of the mistletoe group local reactions such as indurations, oedema, erythema, itching or local pain occurred, which were always only mild to moderate. Serious, life-threatening side effects did not occur. Thus, mistletoe therapy could be considered safe and well tolerated.

Conclusion

The present study demonstrated the safety and efficacy of Iscador as part of a supportive therapy in patients with pancreatic cancer.

Patients in the mistletoe group had significantly fewer side effects caused by conventional therapy, fewer disease-related symptoms, a better general condition, shorter hospitalisation periods and a significantly higher survival rate than patients in the control group.

The mistletoe therapy was well tolerated and could be assessed as safe.

 

Last update: August 17th, 2020/AT

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