Complete, Durable Remission of Advanced Hepatocellular Carcinoma under Treatment with Viscum album Extracts: A Case Report.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths. Early-stage disease is treated with curative intent, but most patients present with advanced HCC, which carries a poor prognosis. Viscum album extracts (VAE) are used by cancer patients as an adjunct treatment or palliation. CASE PRESENTATION: A 51-year-old female presented with relapsing multifocal HCC. She declined palliative treatment and commenced intravenous VAE treatment in conjunction with intravenous hepato-protective L-ornithine-L-aspartate (LOLA). She experienced a significant improvement of life-quality and performance status. After 3 months, a significant regression was noted on computerized tomography, and α-fetoprotein was in normal range. Imaging 11 months later confirmed a complete regression. The VAE and LOLA treatment continues to date. The patient had no other cancer-directed therapy. The regression is sustained for more than 5 years at publication, confirmed by regular imaging and serology. The patient is experiencing an unrestricted quality of life. CONCLUSION: Complete regression of advanced HCC is rare. Responses of HCC to VAE treatment have been reported before. However, this is the first documented case with a complete and durable regression of an HCC under treatment with VAE. Further studies should evaluate VAE treatment in HCC, especially when administered in forms as reported here.

Simple and effective bacterial-based intratumoral cancer immunotherapy.

BACKGROUND: We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer patients. METHODS: Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient. RESULTS: Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas; 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided. CONCLUSION: Our data demonstrate that intratumoral injection of CFA has major antitumor effects in a proportion of treated animals and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumors, and is suitable to patients in developing countries and advanced care settings.

Coley's Lessons Remembered: Augmenting Mistletoe Therapy.

The following four observations point in the same direction, namely that there is an unleveraged potential for stimulating the innate immune system against cancer: (1) experimental treatments with bacterial extracts more than 100 years ago by Coley and contemporaries, (2) a positive correlation between spontaneous regressions and febrile infection, (3) epidemiological data suggesting an inverse correlation between a history of infection and the likelihood of developing cancer, and (4) our recent finding that a cocktail of pattern recognition receptor ligands (PRRLs) can eradicate solid tumors in cancer mice if applied metronomically. Because the main immunostimulating component of mistletoe extract (ME), mistletoe lectin, has been shown to be a PRRL as well, we suggest to apply ME in combination with additional PRRLs. Additional PRRLs can be found in approved drugs already on the market. Therefore, augmentation of ME might be feasible, with the aim of reattaining the old successes using approved drugs rather than bacterial extracts.

Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports.

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 (pT2bcNxM0 follicle center and pT2ac-NxM0 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.

Antecedentes: El muérdago es una planta que se utiliza ampliamente como tratamiento oncológico complementario, por lo general, en forma concomitante con la terapia convencional recomendada. Sin embargo, no se sabe mucho sobre su uso, efectividad y seguridad en el tratamiento del linfoma cutáneo.Caso clínico: Dos pacientes diagnosticados con linfoma cutáneo primario de células B (centro folicular pT2bcNxM0 y zona marginal pT2acNxM0) habían rechazado o pospuesto el tratamiento convencional recomendado para estos casos, y recibieron dosis altas de tratamiento con muérdago, que provoca fiebre. Se administró una combinación de inyección intratumoral, subcutánea e intravenosa (IV), y uno de los pacientes también sufrió hipertermia en todo el cuerpo. Se registró un retroceso del linfoma en un período de 12 y 8 meses, respectivamente. Esto sucedió luego de que se administrara una dosis acumulativa de 12,98 g y 4,63 g de extracto de muérdago, respectivamente. A la fecha, los pacientes se encuentran en etapa de remisión, luego de transcurridos 3 años y medio desde el inicio del tratamiento. Ninguno de ellos recibió tratamiento oncológico convencional durante todo el período de observación.