VaL therapy showed a significant and clinically relevant prolongation of OS. The study findings suggest VaL to be a non-toxic and effective second-line therapy that offers a prolongation of OS as well as less disease-related symptoms for patients with locally advanced or metastatic pancreatic cancer.

In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.

Background:Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia.Patients and Methods:We conducted a prospective randomized open label pilot study with 95 patients randomized into three groups. Two groups received Iscador® M special (IMS) or a different mistletoe preparation, respectively, additionally to chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluoro-uracil (CAF). A control group received CAF with no additional therapy. Here we report the comparison IMS (n = 30) vs. control (n = 31). Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Neutropenia was defined as neutrophil counts <1,000/μl and assessed at baseline and one day before each CAF cycle.Results:In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group. In 12 scores the differences were significant (p < 0.02) and nine scores showed a clinically relevant and significant difference of at least 5 points. Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients (p = 0.182).Conclusions:This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF. CAF-induced neutropenia showed a trend to lower frequency in the IMS group.

Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the secondary objective was neutropenia. Here we report the comparison of HxA (n = 34) versus untreated control (n = 31). Results. In the explorative analysis ten of 15 scores of the EORTC QLQ-C30 showed a better quality of life in the HxA group compared to the control group (P < 0.001 to P = 0.038 in Dunnett-T3 test). The difference was clinically relevant (difference of at least 5 points, range 5.4–12.2) in eight of the ten scores. Neutropenia occurred in 7/34 HxA patients and in 8/31 control patients (P = 0.628). Conclusions. This pilot study showed an improvement of quality of life by treating breast cancer patients with HxA additionally to CAF. Although the open design may be a limitation, the findings show the feasibility of a confirmatory study using the methods described here.

Background: Major surgery suppresses natural killer (NK) cell cytotoxic activity which is potentially harmful for cancer patients by favouring haematogenic tumour cell dissemination. The influence of a perioperative infusion of a standardized mistletoe extract (Iscador ®) on immune functions was tested in a prospective, sequential, randomized clinical trial. Patients and Methods: Colorectal cancer patients undergoing open tumour resection were randomly assigned to either mistletoe infusion or no additional therapy. We hypothesized that mistletoe infusion improves NK cell activity and increases expression of MHC class II antigen HLA-DR on monocytes 24 h and 7 days after surgery, respectively. For statistical analysis we used a sequential study design. The decision boundaries for the two triangular tests were calculated for altogether 62 patients. Results: The sequential study design allowed stopping the recruitment prematurely. NK cell activity differed significantly between the therapy groups 24 h after surgery (p = 0.027). The absolute number of HLA-DR molecules on monocytes did not differ 7 days after surgery. NK cell activity of patients treated with mistletoe extract did not change significantly during the course of the study (-7.9% 24 h after surgery), whereas HLA-DR expression changed significantly (-38.5% at day 7 after surgery). For control patients both parameters decreased significantly after surgery (NK cell activity: -44.4% at 24 h; HLA-DR expression: -32.9% at day 7 after surgery). Conclusion: Perioperative infusion of mistletoe extracts can prevent a suppression of NK cell activity in cancer patients. The impact of this therapy on relapse and survival should be tested in further studies.

Objectives: Evaluate the safety and clinical response of complementary treatment with European mistletoe extracts during chemotherapy.Design: Monocentric controlled trial with 95 patients randomized into three groups.Settings/Location: National Cancer Research Center of Serbia.Subjects: Breast cancer patients (stage T1–3N0–2M0) undergoing surgery and adjuvant chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluorouracil.Interventions: Two different European mistletoe extracts (Helixor A, Iscador M Spez) were injected three times per week during 18 weeks of chemotherapy in the mistletoe group. Five-year follow-up of routine visits was documented in case report forms.Outcome measures: Safety was assessed by measuring adverse events, body temperature during chemotherapy, and probability of relapse or metastasis in a 5-year follow-up. During chemotherapy, the neutrophil count and quality of life according to EORTC QLQ-C30 were assessed.Results: The two patient groups receiving different complementary mistletoe treatments were integrated into one mistletoe group for this safety analysis. Patients in the mistletoe group did not develop more fever symptoms than patients in the control group (two short-term events in each group). No significant differences in probability of relapse or metastasis were measured between the groups (p = 0.7637). The mistletoe group showed a trend toward less neutropenia (p = 0.178) and improved pain and appetite loss scores (p < 0.0001 and p = 0.047, respectively) while having positive, but not significant, impact on other EORTC QLQ-C30 scores.Conclusions: Mistletoe extracts were safe in this clinical study. Neither did subcutaneous injections induce fever, nor did they influence the frequency of relapse and metastasis within 5 years. This result suggests that mistletoe extracts had no adverse interactions with the anticancer agents used in this study. Furthermore, certain side effects of chemotherapy decreased under this complementary treatment in breast cancer patients.

Additional therapy with extracts of Viscum album [L.] (VaL) increases the quality of life of patients suffering from early stage breast cancer during chemotherapy. In the current study patients received chemotherapy, consisting of six cycles of cyclophosphamide, anthracycline, and 5-Fluoro-Uracil (CAF). Two groups also received one of two VaL extracts differing in their preparation as subcutaneous injection three times per week. A control group received CAF with no additional therapy. Six of 28 patients in one of the VaL groups and eight of 29 patients in the control group developed relapse or metastasis within 5 years. Subgroup analysis for hormone- and radiotherapy also showed no difference between groups. Additional VaL therapy during chemotherapy of early stage breast cancer patients appears not to influence the frequency of relapse or metastasis within 5 years.

BackgroundMistletoe extracts have anti-tumor properties and are approved for subcutaneous use in cancer patients. Data on Intravenous application are limited.MethodsAn aqueous extract from pine-mistletoe was used to investigate maximum tolerable dose (MTD) and safety of intravenous application. It was infused once weekly for 3 weeks in patients with advanced cancer. Any type of cancer was included; relevant exclusion criteria were concurrent chemo- or radiation therapy. The classical phase I 3 + 3 dose escalation scheme was followed. Predefined dose groups were 200, 400, 700, 1200 and 2000 mg. Maximum planned dose was 2000 mg. With the MTD three more patients should be treated for 9 weeks in order to evaluate intermediate term tolerability. Weekly during the treatment and 1 week later tolerability, clinical status, safety laboratory parameters and adverse events were documented.ResultsTwenty-one patients (3 in the dose groups 200, 400, 700 and 1200 mg, respectively, 9 in the dose group 2000 mg) were included. MTD was not reached. Because one dose-limiting toxicity (DLT), an allergic reaction, occurred during infusion of 2000 mg, three more patients had to be included in this dose group and tolerated it, as well as the three patients who received 2000 mg for 9 weeks. Occasionally in the dose group 2000 mg mild to moderate fever occurred.ConclusionWeekly infusions of 2000 mg of the pine-mistletoe extract were tolerated and can be used in further studies but had a risk for allergic reactions and fever. German Clinical Trials Register (Trial registration number DRKS00005028).