[Mistletoe extract for treatment of urological tumors]

Abstract

Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma.

Case Report: Two patients with primary cutaneous B-cell lymphoma (pT_2bcN_xM₀ follicle center and pT_2ac-N_xM₀ marginal zone) either declined or postponed recommended conventional treatment and received high-dose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia. The lymphoma regressed over a period of 12 and 8 months, respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g mistletoe extract, respectively. The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period.

Key Words: Mistletoe treatment, Lymphoma, primary cutaneous B-cell lymphoma, fever, PCBCL, PCFCL, PCMZL, cancer, tumor

Long-term remissions of lymphoma after fever-inducing therapy with bacterial toxins have been documented since William Coley.¹ Primary cutaneous lymphomas make up about 5% of all non-Hodgkin's lymphoma (annual incidence, 1:100 000); 20% to 25% of these are primary cutaneous B-cell lymphomas (PCBCL).^2–4 The most common subtypes are primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and diffuse large cell lymphoma. The follicle center and marginal zone B-cell lymphomas tend to be indolent and have a 5-year survival of more than 95%⁵; although relapses are common, systemic progression is rare. Single lesions are treated with radiotherapy, intralesional steroids, surgical excision, or a “wait and see” strategy. Multifocal or relapsed systemic disease is usually treated with rituximab (R, anti-CD20 monoclonal antibody), single- or multi-agent chemotherapy (eg, chlorambucil or cyclophosphamide; vincristine; prednisolone; cyclophosphamide, vincristine, and predisolone [CVP]), or immunotherapy with interferon-α.^6,7 PCBCL is associated with immune dysregulation and in some instances immunodeficiency with chronic inflammation (particularly PCMZL), eg, in rheumatoid arthritis or Sjügren's syndrome and with Borrelia burgdorferi infection.^8–12 They respond to immunological treatments like intralesional injections of interferon-α¹³ or adenovirus-encoding interferon-γ, which can even lead to remission in non-injected distant lesions.¹⁴ Survival in systemic lymphoma correlates with tumor-infiltrating immune cells,¹⁵ and for the occasionally observed spontaneous regressions of non-Hodgkin's lymphoma, immunologic mechanisms have been proposed.^16,17

Mistletoe extract (ME) is a whole plant remedy derived from Viscum album L, a hemi-parasitic shrub; it is widely used for complementary cancer treatment, especially in Europe, in conjunction with conventional therapy.¹⁸ A variety of biologically active compounds have been isolated from ME, including mistletoe lec-tins (MLs), viscotoxins, oligo- and polysaccharides, and others.^19,20 ME has immunostimulatory activity (in vivo and in vitro activation of monocytes/macrophages, granulocytes, natural killer cells, T-cells, dendritic cells, induction of a variety of cytokines^19,20), and several compounds (ML in particular) are cytotoxic with established apoptosis-inducing effects.^19–21

ME is usually applied subcutaneously at a low starting dose, which is slowly titrated upwards and adjusted individually. This approach is associated with improvement of quality of life and probably also survival.^22–24 Tumor remission has rarely been observed with low dosages, but mainly after high, fever-inducing ME dosage, often injected intratumorally or as an intravenous (IV) infusion.^22–24 However, these observations have been reported only in case series and case reports.^23–27 No randomized trials have yet investigated the role of ME in the treatment of lymphoma. Apart from dose-dependent flu-like symptoms, fever, and inflammatory reactions at the injected sites, ME treatment is safe. Occasionally, hyper-sensitivity reactions are reported.²⁸

Two patients with primary cutaneous lymphoma were treated at the Park Attwood Clinic (PAC, which closed in 2010), a British center specializing in complementary cancer care and particularly in high-dose and fever-inducing ME treatment. Informed consent for ME treatment was obtained from both patients with the understanding that this would not replace recommended therapies and there was good evidence that ME could improve tolerance of mainstream treatment when applied concurrently.

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