Estudios de Seguridad del Medicamento

Buena tolerabilidad

Bar-Sela, G. White-Berry Mistletoe (Viscum album L.) as complementary treatment in cancer: Does it help? European Journal of Integrative Medicine 2011;3:e55-e62. DOI: 10.1016/j.eujim.2011.03.002

Melzer J. et al. Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forsch Komplementmed, 2009;16:217-226. DOI:10.1159/000226249.

Kienle GS, Kiene H. Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther, 2010;9:142-157. DOI: 10.1177/1534735410369673.

Steele ML. et al. Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients. Evid Based Complement Alternat Med, 2014;2014:724258. DOI: 10.1155/2014/724258

Eventos no deseados generalmente solo son leves; no se observaron eventos graves o que amenacen la vida

Horneber MA, et al. Mistletoe therapy in oncology. Cochrane Database Syst Rev, 2008:CD003297. DOI: 10.1002/14651858.CD003297.pub2

Augustin M. et al. Safety and efficacy of the long-term adjuvant treatment of primary intermediate- to high-risk malignant melanoma (UICC/AJCC stage II and III) with a standardized fermented European mistletoe (Viscum album L.) extract. Results from a multicenter, comparative, epidemiological cohort study in Germany and Switzerland. Arzneimittelforschung, 2005; 55(1):38-49. DOI: 10.1055/s-0031-1296823.

Gunver S. et al. Safety of higher dosages of Viscum album L. in animals and humans–systematic review of immune changes and safety parameters. BMC Complement Altern Med, 2011 Aug 28;11:72. DOI: 10.1186/1472-6882-11-72.

Para mayor información y más estudios sobre la Seguridad del medicamento: Terapiademuerdago.com

Estudios sobre la Calidad de vida

Efecto positivo sobre la calidad de vida en pacientes que reciben quimioterapia junto con la Terapia de Muérdago comparados con los que solo reciben quimioterapia

Kienle G S and Kiene H. Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther, 2010;9:142-157. DOI: 10.1177/1534735410369673 

Lange-Lindberg AM et al. Mistletoe treatments for minimising side effects of anticancer chemotherapy. GMS Health Technol Assess 2006;2:Doc18. PMID: 21289969

Horneber MA et al. Mistletoe therapy in oncology. Cochrane Database Syst Rev, 2008:CD003297. DOI: 10.1002/14651858.CD003297.pub2

Loef M, Walach H. Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis. pre-print published at medRxiv.org [Internet]. 2019. DOI: 10.1101/19013177

Sociedades científicas como la Society for Integrative Oncology (SIO) y la American Cancer Society (ASCO) reconocen el efecto positivo sobre la calidad de vida asociada al uso de la Terapia de Muérdago

Greenlee H et al. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment. CA Cancer J Clin, 2017;67:194-232. DOI: 10.3322/caac.21397

Lyman GH et al. Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline. J Clin Oncol, 2018;36:2647-2655. DOI: 10.1200/JCO.2018.79.2721

Mejora considerable de la autorregulación (equilibrio interno, sentimiento de competencia y seguridad en situaciones de estrés)

Grossarth-Maticek R. et al. Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 2001;7:57-66, 68-72. PMID: 11347286

Bar-Sela G. et al. Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: a randomised phase II study. Eur J Cancer, 2013;49:1058-1064 DOI: 10.1016/j.ejca.2012.11.007

Büssing A. et al. Validation of the self-regulation questionnaire as a measure of health in quality of life research. Eur J Med Res 2009;14:223-227. DOI: 10.1186/2047-783x-14-5-223

Mejora significativa de los síntomas asociados al síndrome de fatiga debido a la enfermedad o la terapia estándar

Tröger W et al. Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone. Breast Cancer, 2009;16:35-45. DOI: 10.4137/bcbcr.s2905

Kienle GS et al. Intravenous Mistletoe Treatment in Integrative Cancer Care: A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors. Evid Based Complement Alternat Med, 2016;2016:4628287. DOI: 10.1155/2016/4628287

Tröger W et al. Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. Dtsch Arztebl Int, 2014;111:493-502, 433 p following 502. DOI: 10.3238/arztebl.2014.0493

Para mayor información y más estudios sobre la Calidad de Vida y a Terapia de Muérdago: Terapiademuerdago.com

Estudios sobre combinación con otras terapias

La Terapia de muérdago a menudo se administra en paralelo con la quimioterapia o radioterapia para mejorar su tolerabilidad y para aliviar los síntomas debido a la enfermedad y a la terapia:

Jeong-Heum B et al. Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study. World J Surg Onc 19, 178 (2021). DOI: 10.1186/s12957-021-02293-4

Friedel WE. et al. Systematic evaluation of the clinical effects of supportive mistletoe treatment within chemo- and/or radiotherapy protocols and long-term mistletoe application in nonmetastatic colorectal carcinoma: multicenter, controlled, observational cohort study. J Soc Integr Oncol. 2009 Fall;7(4):137-45. PMID: 19883529.

Kienle G S and Kiene H. Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther, 2010;9:142-157. DOI: 10.1177/1534735410369673 

Piao BK et al. Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial. Anticancer Res. 2004 Jan-Feb;24(1):303-9. PMID: 15015612

Bock PR. Et al. [Efficacy and safety of long-term complementary treatment with standardized European mistletoe extract (Viscum album L.) in addition to the conventional adjuvant oncologic therapy in patients with primary non-metastasized mammary carcinoma. Results of a multi-center, comparative, epidemiological cohort study in Germany and Switzerland]. Arzneimittelforschung. 2004;54(8):456-66. German. DOI 10.1055/s-0031-1296999. 

Tröger W. et al. Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone. Breast Cancer (Auckl). 2009 Jul 6;3:35-45. DOI: 10.4137/bcbcr.s2905. PMID: 21556248.

Los experimentos de cultivo celular indican que no existen riesgos cuando se combina fármacos quimioterapéuticos y preparados farmacéuticos de muérdago. 

Weissenstein U. et al. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro. BMC Complement Altern Med. 2014 Jan 8;14:6. DOI: 10.1186/1472-6882-14-6. PMID: 24397864

Burkhart J. Et al. In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide. Altern Ther Health Med. 2010 May-Jun;16(3):40-8. PMID: 20486623.

Schink M, Dehus O. Effects of mistletoe products on pharmacokinetic drug turnover by inhibition and induction of cytochrome P450 activities. BMC Complement Altern Med. 2017 Dec 4;17(1):521. DOI: 10.1186/s12906-017-2028-1. PMID: 29202738

Experimentos in vitro mostraron que los preparados de muérdago protegen a las células humanas sanas del sistema inmune, pero no a las células malignas (células malignas Jurkat), ante los efectos citostáticos de la quimioterapia (4-hidroperoxiciclofosfamida).

Burkhart J. Et al. In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide. Altern Ther Health Med. 2010 May-Jun;16(3):40-8. PMID: 20486623.

Actividad citotoxicidad sinérgica in vitro en la combinación de preparados farmacéuticos de muérdago y quimioterapia:

Pae HO. Et al. Mistletoe lectin synergizes with paclitaxel in human SK-hep1 hepatocarcinoma cells. Immunopharmacol Immunotoxicol. 2001 Nov;23(4):531-40. DOI: 10.1081/iph-100108599. PMID: 11792012.

Siegle I. Et al. Combined cytotoxic action of Viscum album agglutinin-1 and anticancer agents against human A549 lung cancer cells. Anticancer Res. 2001 Jul-Aug;21(4A):2687-91. PMID: 11724340.

Para mayor información y más estudios sobre la Terapia de Muérdago y la combinación con otras terapias: Terapiademuerdago.com

Estudios de evidencia clínica

METAANÁLISIS Y REVISIONES SISTEMÁTICAS

Existe toda una serie de metaanálisis y revisiones sistemáticas sobre la terapia de muérdago en enfermedades oncológicas con diferente metodología sistemática. Revisar los estudios en: Terapiademuerdago.com

ESTUDIOS CLÍNICOS

Sobre los preparados farmacéuticos antroposóficos de muérdago abnobaVISCUM®, Helixor®, Iscador® e Iscucin®, actualmente hay 157 estudios disponibles (estado a octubre 2021):

34 estudios clínicos prospectivos aleatorizados (RCTs, por sus siglas en ingles)

20 estudios comparativos prospectivos no aleatorizados

51 estudios comparativos retrospectivos

52 estudios de cohortes o pequeñas series de casos (comparativo antes-después).

Como resultado, 152 de 157 estudios (= 97%) muestran una ventaja para la terapia de muérdago.

Para mayor información y revisión, los resultados de los estudios clínicos según entidades tumorales: Terapiademuerdago.com

INVESTIGACIÓN DE SERVICIOS DE SALUD

Los estudios de servicios de salud o bien Real-Word Data (RWD) ganan cada vez más importancia en la oncología moderna y son también reconocidos internacionalmente. Los resultados de los estudios RWD sobre muérdago se pueden resumir de la siguiente manera:

Implementación y seguridad

Las terapias oncológicas de medicina integrativa son muy aceptadas por pacientes oncológicos de diferentes edades y son implementables en la atención diaria de los servicios de salud de los centros oncológicos certificados por la Sociedad Alemana del Cáncer

Thronicke A. et al. Integrative cancer care in a certified Cancer Centre of a German Anthroposophic hospital. Complement Ther Med. 2018 Oct;40:151-157. DOI: 10.1016/j.ctim.2018.03.012. Epub 2018 Apr 4. PMID: 30219441.

Schad F. et al. Implementation of an Integrative Oncological Concept in the Daily Care of a German Certified Breast Cancer Center. Complement Med Res. 2018;25(2):85-91. DOI: 10.1159/000478655. Epub 2018 Mar 7. PMID: 29510405.

La terapia subcutánea de muérdago, así como, el uso intravenoso e intratumoral (ambos off label) en combinación con otras terapias tumorales, es segura y tiene un perfil de efectos secundarios de leve a moderado.

Steele ML. et al. Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients. Evid Based Complement Alternat Med. 2014;2014:724258. DOI: 10.1155/2014/724258. Epub 2014 Jan 19. PMID: 24672577

Steele ML. et al. Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study. Evid Based Complement Alternat Med. 2014;2014:236310. doi: 10.1155/2014/236310. Epub 2014 May 15. PMID: 24955100

Steele ML. et al. Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology. Integr Cancer Ther. 2015 Mar;14(2):140-8. DOI: 10.1177/1534735414563977. Epub 2014 Dec 30. PMID: 25552476.

Schad F. et al. Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients. Phytomedicine. 2017 Dec 1;36:54-58. DOI: 10.1016/j.phymed.2017.09.004. Epub 2017 Sep 21. PMID: 29157828.

Calidad de vida

Thronicke A. et al. Financial Burden of Lung and Breast Cancer Patients as an Early Indicator of Emotional and Physical Burden – a Prospective Real-World Data (RWD). Die Mistel in der Tumortherapie 5, Aktueller Stand der Forschung und klinische Anwendung. Essen: KVC Verlag; 2020. p. 211

Thronicke A. et al. Health-Related Quality of Life in Patients with Lung Cancer Applying Integrative Oncology Concepts in a Certified Cancer Centre. Evid Based Complement Alternat Med. 2020;2020:5917382

Oei SL. Et al. Impact of Oncological Therapy and Viscum album L Treatment on Cancer-Related Fatigue and Internal Coherence in Nonmetastasized Breast Cancer Patients. Integrative Cancer Therapies Volume 19: 1 –16. DOI: 10.1177/1534735420917211

Beuth J. et al. Impact of complementary treatment of breast cancer patients with standardized mistletoe extract during aftercare: a controlled multicenter comparative epidemiological cohort study. Anticancer Res. 2008 Jan-Feb;28(1B):523-7. PMID: 18383896.

Supervivencia prolongada

Schad F. et al. Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis. PloS one, 2018;13:e0203058. DOI:10.1371/journal.pone.0203058

Axtner J. et al. Health services research of integrative oncology in palliative care of patients with advanced pancreatic cancer. BMC Cancer, 2016;16:579. DOI:10.1186/s12885-016-2594-5

Spahn G. et al. An integrative approach of pancreatic carcinoma treatment using Viscum therapy – Results from the clinical register at the Clinic Öschelbronn 2007-2010. Scheer R, Alban S, Becker H, Blaschek W, Kemper F, W K, et al., editors: KVC Verlag, Karl und Veronica Carstens-Stiftung, Essen, 2013, 265-277 p

Pruebas de costos / eficacia

Thronicke A. et al. Cost-Effectiveness of Real-World Administration of Concomitant Viscum album L. Therapy for the Treatment of Stage IV Pancreatic Cancer. Evid Based Complement Alternat Med, 2020. 2020: p. 3543568. DOI: 10.1155/2020/3543568

Thronicke A. et al. Cost-effectiveness of real-world administration of chemotherapy and add-onViscum album L. therapy compared to chemotherapy in the treatment of stage IV NSCLC patients. Plos one, 27 Jul 2020, 15(7):e0236426. DOI: 10.1371/journal.pone.0236426

Producción científica propia del CMA