Hintergrund: Orale maligne Melanome (OMM) des Hundes zeichnen sich durch schnelles Wachstum, lokale Invasion und hohe Metastasierungsraten aus. Extrakte auf Basis von Viscum album L. (VAE) werden zunehmend in der Krebstherapie sowohl in der Human- als auch in der Veterinärmedizin eingesetzt. Ziel unserer Studie war es zu untersuchen, inwieweit die adjuvante Therapie mit VAE eine therapeutische Option zur Behandlung von OMM ist. Besonderes Augenmerk galt dabei der Überlebenszeit und möglichen Nebenwirkungen. Tiere und Methoden: 26 Hunde mit OMM, die in einem der größten veterinäronkologischen Zentren der Schweiz allesamt eine Strahlentherapie erhielten (teilweise nach operativer Tumorresektion) wurden in die retrospektive Studie eingeschlossen: 18 Hunde wurden mit VAE behandelt (1 ml VAE (Iscador®) in ansteigenden Konzentrationen von 0,1 bis 20 mg/ml subkutan 3-mal pro Woche (VAE-Gruppe), 8 erhielten keine adjuvante Behandlung (Vergleichsgruppe). Wir verglichen die Größenentwicklung der OMM sowie die Überlebenszeit. Ergebnisse: Patienten mit Bestrahlung und adjuvanter VAE-Therapie zeigten mit 236 Tagen eine signifikant längere mediane Überlebenszeit im Vergleich zu Patienten mit Bestrahlung, aber ohne adjuvante VAE-Therapie (49 Tage; Log-Rank-Test: p = 0,0047). Die VAE-Therapie verlängerte die Überlebenszeit um mehr als zwei Drittel (Hazard Ratio (HR) = 0,30, 95%-Konfidenzintervall (KI) 0,11-0,86; p = 0,024), während ein höheres Tumorstadium gemäß UICC (Union internationale contre le cancer) einen statistischen Trend zur Verdopplung des Sterberisikos zeigte (UICC-Stadium III/IV vs. I/II: HR = 2,12, 95%-KI 0,88-5,12; p = 0,095). Zwei Patienten zeigten milde Nebenwirkungen während der VAE-Behandlung. Einer der beiden zeigte 1 Tag lang ein selbstlimitiertes Fieber, bei dem anderen Patienten reduzierten wir die Dosis von einem konzentrierteren zu einem weniger konzentrierten VAE (Serie 0) aufgrund von Müdigkeit, die daraufhin verschwand. Schlussfolgerungen: VAE ist eine sichere, nebenwirkungsarme Behandlung und scheint sich positiv auf die Überlebenszeit von Hunden mit OMM auszuwirken. Somit ist dieser therapeutische Ansatz es wert, vermehrt bei der adjuvant zur Strahlentherapie eingesetzten Behandlung des OMM in Betracht gezogen zu werden. Die verglichenen Gruppen waren jedoch klein, divers und nicht konsistent hinsichtlich aller prognostischen Parameter. Eine prospektive Studie mit einer größeren Studienpopulation wäre daher von Interesse.

Keywords Canine mammary tumor · Mistletoe therapy · Viscum album · Adjuvant treatment · Veterinary medicine · Quality of life · Oncology Summary Postsurgical Adjuvant Treatment with Mistletoe Extract (Viscum album ssp. album) in Canine Mammary TumorsBackground: The high incidence rate and malignancy of canine mammary tumors (CMTs) and their treatment pose a challenge in veterinary practice. Postsurgical therapy is required. Currently, there is no established standardized postsurgical adjuvant therapy and such a therapy is not expected for the near future. Maintaining or increasing the dogs' quality of life (QL) and their tolerance of the treatment are of importance to the pet owner. Cancer treatment by using extracts of European mistletoe (Viscum album L.; VAE) is well introduced in human medicine. Besides tumor baseline therapy using radiation or chemotherapy, treatment with VAE is one of the most common adjuvant methods among complementary and alternative therapies. Also in veterinary oncology, Viscum preparations have been used successfully for many years in various species. A number of studies underlined the positive effects of mistletoe treatment in animals. Methods: In the present study, the effects and benefits of postsurgical adjuvant therapy with VAE in canine mammary adenocarcinomas were investigated. Additionally, effects on QL were analyzed. For this purpose, a total of 56 female dogs were enrolled in the study. Of these, 33 dogs served as retrospective control group whereas 23 dogs were assigned as prospective VAE treatment group. The latter started VAE after surgical tumor excision. Results: The median survival time (MST) for all involved dogs (n = 56) was 32 months (interquartile range 13-51 months). For the control group, Kaplan-Meier analysis showed survival of 24 (73%), 20 (61%), 15 (45%), and 5 dogs (12%) after 12, 24, 36, and 48 months, respectively. In the Viscum group, survival was 19 (83%), 14 (61%), 11 (48%), and 1 dog (4%), respectively. Multivariate Cox proportional hazard analysis resulted in a lower death risk after VAE treatment (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.22-1.26), which was not significantly different between the two groups (p = 0.151). An also not significant tendency of decrease in tumor-related death risk to 25% (HR 0.251, 95% CI 0.056-1.122; p = 0.07) was observed for the treatment group. Conclusions: The results indicate a tendency of lower tumor-related death risk after postsurgical adjuvant VAE therapy in female dogs suffering from CMTs. The QL was stable during the entire observation period and the therapy was well tolerated by the patients. (HR 0,251,122). Schlussfolgerungen: Es kann eine Tendenz zur Senkung des tumorbedingten Sterberisikos der VAEGruppe bei guter Verträglichkeit der Therapie angenommen werden. Die LQ der Tiere blieb über die gesamte Beobachtungszeit auf hohem Niveau stabil.

Cancer is a common disease in humans and in companion animals and treatment is challenging. The aim of this systematic review was to identify and assess the potential use of Viscum album L. extracts (VAE) for treatment of neoplastic diseases in companion animals. Peer-reviewed animal, in vivo and in vitro studies were included, considering the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and a measurement tool to assess systematic reviews (AMSTAR). Overall, 6,148 references were identified. Following a predefined protocol, 114 full-text references were assessed. Ultimately, 61 references were included for further assessment, 25 references included in vitro experiments, 26 included in vivo and clinical experiments and 10 references included both in vitro and in vivo experiments. These 61 references comprised data of 193 in vitro and 67 in vivo and clinical experiments. Most of the 67 in vivo and clinical experiments were conducted with mice (59), followed by rats (4), dogs (3) and horses (1). So far, oral melanomas, mammary tumors and sticker sarcomas in dogs, as well as sarcoids in horses, have been investigated in controlled clinical trials. A scoring system was established to evaluate the outcomes of each study based on defined effect levels. The efficacy of VAE treatment was most pronounced for melanomas, sarcomas, mammary carcinoma and equine sarcoids. The limited number and quality of published studies on VAE treatment in companion animals impedes to draw definitive conclusions regarding the efficacy of VAE in the treatment of cancer. Thus, further research is needed to elucidate the impact of VAE on the treatment of cancer in companion animals and possible underlying mechanisms.

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