Mistletoe, a semiparasitic plant, holds interest as a potential anticancer agent because extracts derived from it have been shown to kill cancer cells in vitro [1-10] and to stimulate immune system cells both in vitro and in vivo .[10-24] Two components of mistletoe, namely viscotoxins, polysaccharides and lectins, may be responsible for these effects.[10-13,17-19,21-23,25-32] Viscotoxins are small proteins that exhibit cell-killing activity and possible immune-system-stimulating activity.[1,6,18,19,33,34] Lectins are complex molecules made of both protein and carbohydrates that are capable of binding to the outside of cells (e.g., immune system cells) and inducing biochemical changes in them.[10,35-38] In view of mistletoe’s ability to stimulate the immune system, it has been classified as a type of biological response modifier. Biological response modifiers constitute a diverse group of biological molecules that have been used individually, or in combination with other agents, to treat cancer or to lessen the side effects of anticancer drugs. Mistletoe extracts have been demonstrated in preclinical settings to have other mechanisms of action, such as antiangiogenesis.
Preparations from mistletoe extracts are most frequently used in the treatment of cancer patients in German-speaking countries. Commercially available extracts are marketed under a variety of brand names, including Iscador (see explanation of suffixes below), Eurixor, Helixor, Isorel, Iscucin, Plenosol, and abnobaVISCUM. Some extracts are marketed under more than one name. Iscador, Isorel, and Plenosol are also sold as Iscar, Vysorel, and Lektinol, respectively. All of these products are prepared from Viscum album (Loranthaceae) (Viscum album L. or European mistletoe). They are not sold as a drug in the United States.
Mistletoe grows on several types of trees, and the chemical composition of extracts derived from it depends on the species of the host tree (e.g., apple, elm, oak, pine, poplar, and spruce), the time of year harvested, how the extracts are prepared, and the commercial producer.[8,36,46-49]
Mistletoe extracts are prepared as aqueous solutions or solutions of water and alcohol, and they can be fermented or unfermented.[4,6,20,46,47,50-53] Some extracts are prepared according to homeopathic principles, and others are not. Accordingly, as homeopathic preparations, they are typically not chemically standardized extracts.[10,54] In addition, the commercial products can be subdivided according to the species of host tree, which is typically indicated in the product name by a suffix letter. Iscador, a fermented aqueous extract of Viscum album L. that is prepared as a homeopathic drug, is marketed as IscadorM (from apple trees; Malus domestica), IscadorP (from pine trees; Pinus sylvestris), IscadorQ (from oak trees; Quercus robur), and IscadorU (from elm trees; Ulmus minor). Helixor, an unfermented aqueous extract of Viscum album L. that is standardized by its biological effect on human leukemia cells in vitro, is marketed as HelixorA (from spruce trees; Picea abies), HelixorM (from apple trees), and HelixorP (from pine trees; Pinus sylvestris). Eurixor, an unfermented aqueous extract of Viscum album L. harvested from poplar trees, is reportedly standardized to contain a specific amount of one of mistletoe’s lectins (i.e., the lectin ML-1; refer to the History section of this summary for more information). Some proponents contend the choice of extract should depend on the type of tumor and the gender of the patient.[49,51,55,56]
A recombinant ML-1 from Escherichia coli bacteria known as rViscumin or aviscumine has been studied in the laboratory and in phase I clinical trials. Since this is not an extract of mistletoe, it is out of the purview of this summary.
Mistletoe extracts are usually given by subcutaneous injection, although administration by other routes (i.e., oral, intrapleural, intratumoral, and intravenous) has been described.[17,20-24,32,36,49,51,54,58-63] In most reported studies, subcutaneous injections were given 2 to 3 times a week, but the overall duration of treatment varied considerably.
Viscum album is listed in the Homeopathic Pharmacopoeia of the United States, which is the officially recognized compendium for homeopathic drugs in this country. Although the U.S. Food and Drug Administration (FDA) has regulatory authority over homeopathic drugs, this authority is usually not exercised unless the drugs are formulated for injection or there is evidence of severe toxicity. At present, the FDA does not allow the importation or distribution of injectable preparations of mistletoe, including homeopathic formulations, except for the purpose of clinical research. The extracts are not available commercially in the United States and are not approved as a treatment for people with cancer.
Before researchers can conduct clinical drug research in the United States, they must file an Investigational New Drug (IND) application with the FDA. IND approval is also required for clinical investigation of homeopathic drugs. The FDA does not disclose information about IND applications or approvals; this information can be released only by the applicants. At least two U.S. investigators were given IND approval to study mistletoe as a treatment for people with cancer (NCCAM-02-AT-260 and TJUH-01F.45).
In this summary, the mistletoe extract or product used in each study will be specified wherever possible.
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