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Introduction: Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) belong to the group of keratinocyte carcinomas (KC). Actinic keratosis (AK) is a precursor lesion of cSCC. The incidences of cSCC, BCC, and AK are currently strongly increasing. Different standard therapies exist for these conditions but are not always applicable or successful. Hydrophilic Viscum album extracts have been used in anthroposophic cancer therapy since 1917. Viscum album lipophilic extract (VALE) is prepared by means of supercritical CO2 extraction. This retrospective case series assessed the safety and clinical effects of a topical application of 10% VALE in individual cases of cSCC, BCC, and AK., Methods: For this retrospective case series, a positive vote was obtained from the Ethics Committee of the University of Witten/Herdecke (No. 146/2020). Eligible patients signed a declaration of consent prior to inclusion in the study. The main outcome parameters were the clinical response to treatment with VALE and adverse drug reactions. Risk factors, concomitant therapies and diseases, further diagnostic and therapeutic information were documented where available. Data analysis was performed on the level of patients and of individual lesions., Results: The study population consisted of 55 patients with 74 skin lesions. Individual case analysis accompanied by photographic documentation revealed typical and promising treatment courses. Clinical response rates (complete + partial remissions) for individual lesions were 78% for cSCC, 70% for BCC, and 71% for AK. Complete remission rates for individual lesions were 56% for cSCC, 35% for BCC, and 15% for AK. In cSCC and BCC, shorter times to best clinical response were observed. Adverse drug reactions were reported in 5 patients including erythema and inflammatory reactions of mostly moderate severity that resolved completely. In one case, therapy was temporarily paused, in four cases it was continued without interruption., Discussion/conclusion: The results of this study suggest that VALE is a safe and tolerable extract under whose application complete and partial remissions of KC could be observed. To improve and assess the efficacy of VALE, prospective investigations are necessary., Das kutane Plattenepithelkarzinom (cSCC) und das Basalzellkarzinom (BCC) gehören zur Gruppe der Keratinozytenkarzinome (KC). Die aktinische Keratose (AK) ist eine Vorstufe des cSCC. Die Häufigkeit von cSCC, BCC und AK ist derzeit stark im Steigen begriffen. Es gibt verschiedene Standardtherapien für diese Erkrankungen, die jedoch nicht immer anwendbar oder erfolgreich sind. Hydrophile Viscum album-Extrakte werden seit 1917 in der anthroposophischen Krebstherapie eingesetzt. Viscum album Lipophilic Extract (VALE) wird mittels überkritischer CO2-Extraktion hergestellt. In dieser retrospektiven Fallserie wurden die Sicherheit und die klinischen Auswirkungen einer topischen Anwendung von 10% VALE bei einzelnen Fällen von cSCC, BCC und AK untersucht.Für diese retrospektive Fallserie wurde ein positives Votum der Ethikkommission der Universität Witten/Herdecke eingeholt (Nr. 146/2020). Die in Frage kommenden Patienten unterzeichneten vor der Aufnahme in die Studie eine Einverständniserklärung. Die wichtigsten Ergebnisparameter waren das klinische Ansprechen auf die Behandlung mit VALE und unerwünschte Arzneimittelwirkungen. Risikofaktoren, Begleittherapien und -erkrankungen sowie weitere diagnostische und therapeutische Informationen wurden, soweit vorhanden, dokumentiert. Die Datenanalyse wurde für jeden einzelnen Patienten und jeder einzelnen Läsion durchgeführt.Die Studienpopulation bestand aus 55 Patienten mit 74 Hautläsionen. Die Einzelfallanalyse mit Fotodokumentation ergab typische und vielversprechende Behandlungsverläufe. Die klinischen Ansprechraten (vollständige + partielle Remissionen) für einzelne Läsionen lagen bei 78% für cSCC, 70% für BCC und 71% für AK. Die Komplettremissionsraten für einzelne Läsionen lagen bei 56% für cSCC, 35% für BCC und 15% für AK. Bei cSCC und BCC wurden kürzere Zeiten bis zum besten klinischen Ansprechen beobachtet. Bei fünf Patienten wurden unerwünschte Arzneimittelwirkungen gemeldet, darunter Erytheme und Entzündungsreaktionen von meist mäßigem Schweregrad, die vollständig abklangen. In einem Fall wurde die Therapie vorübergehend pausiert, in vier Fällen wurde sie ohne Unterbrechung fortgesetzt.Die Ergebnisse dieser Studie deuten darauf hin, dass VALE ein sicherer und verträglicher Extrakt ist, bei dessen Anwendung vollständige und partielle Remissionen von KC beobachtet werden konnten. Um die Wirksamkeit der Therapie mit VALE weiterzuentwickeln und eingehender zu beurteilen, sind prospektive Untersuchungen erforderlich., (© 2024 S. Karger AG, Basel.)

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 T 1-3 N 0-2 M 0 ) 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.

Background: Mistletoe extracts have anti-tumor properties and are approved for subcutaneous use in cancer patients. Data on Intravenous application are limited., Methods: An 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., Results: Twenty-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., Conclusion: Weekly 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).

Background: The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract., Method: An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated., Results: Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to -17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial., Conclusion: 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: In a previous study a decline of T-lymphocyte function was observed within a 6-month period of Viscum album extract (VA-E) application which did not occur in those patients with dose adaptation in response to strong local reactions (LR) or in those with moderate LR. To further investigate the immunological prerequisites of these differences in the VA-E susceptibilities, an analysis was carried out of the pre-existing differences in the tumor patients' lymphocyte subsets, and of whether the LR pattern (none, moderate, strong) might be associated with distinct aspects of the patients' quality of life., Patients and Methods: Seventy-one cancer patients were subcutaneously treated with VA-E (Iscador) at increasing concentrations and their lymphocyte subsets measured by flowcytometry during a 6 month observation period; quality of life was assessed with the HLQ questionnaire., Results: The occurrence of stronger LR was associated with a primarily higher level of T-cells and their CD4+ T-helper/inducer subset, and CD25+ respectively HLA-DR+ (activated) T-cells. Moreover, counts or proportions of T-cells, CD4+ T-helper/inducer cells and CD8+ CD28+ cytotoxic cells were lower, while the relative proportions of CD8+ CD28- suppressor cells, B- and NK-cells were the highest in the group with moderate LR. In particular, this latter group had a significantly higher quality of life., Conclusion: Our results indicate that the induction of moderate LR in response to VA-E application was associated with better T cell function and quality of life. Extracts from Viscum album (VA-E) are widely used as a

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.

Background: Suppression of NK cell activity is considered to be an unfavourable prognostic factor for tumour progression. There is proof that mistletoe extracts may increase NK cell activity. However, the inverse relation between an increase of NK cell activity and clinical progress of cancer has not been investigated., Aim and Design: The relation of NK cell activity and progress of cancer in patients under therapy with mistletoe extracts was examined in a prospective, monocentric, cohort study. At the same time the in vitro killing of K562 cells and autologous tumour cells was compared., Patients and Methods: 40 patients with operable cancer of the breast or colon were included. The patients did not receive any immunologically relevant therapies except for mistletoe extracts. The absolute NK cell count in peripheral blood as well as the in vitro NK cell activity were monitored for up to 2 years and compared with clinical outcome as well as quality of life., Results: The absolute NK cell count in peripheral blood increased within the observation period. Patients without progression had a significantly higher mean activity of NK cells against K562 cells than patients with progression. In the latter group, only stage IV patients showed reduced NK cell activity. The killing activity against autologous tumour cells was <5% in about 77.5% of the patients and could not be evaluated further. The NK cell activity against K562 cells was not related to the number of NK cells., Conclusions: We found a relation between NK cell activity and the progression of malignant disease. In further studies the causality of this relation has to be clarified. The establishment of NK cell activity against autologous tumour cells as a suitable parameter during follow-up was not successful.