Clinical Studies with Mistletoe Lectin

Cellular Immunomodulation and Safety of Standardized Aqueous Mistletoe Extract..., The Standardised Mistletoe Extract PS76A2 Improves QoL in Patients with Breast Cancer.

Cellular Immunomodulation and Safety of Standardized Aqueous Mistletoe Extract PS76A2 in Tumor Patients Treated for 48 Weeks

W. DOHMEN(1), M. BREIER(1) and U. MENGS(2)
(1) Academical Practice of General Medicine, Medical Faculty, RWTH Aachen, Thomashofstrasse 3, D-52070 Aachen;
(2) MADAUS AG, D-51101 Cologne, Germany
Key Words: Standardized aqueous mistletoe extract, mistletoe lectin, oncology, immunomodulation, tolerability, tumor patients.
Running title: Immunomodulation by Mistletoe Extract
Correspondence to: Dr. Ulrich Mengs, MADAUS AG, D-51101 Cologne, Germany.
Tel: (+) 49-221-8998-251, Fax: (+) 49-221-8998-1251, e-mail: u.mengs@madaus.de
Abstract: Non-selected tumor patients (n=12) with various solid carcinomas were treated continuously twice weekly over 48 weeks with the aqueous mistletoe extract PS76A2, standardized to active mistletoe lectin. The preparation was applied subcutaneously at a concentration of 15 ng mistletoe lectin per 0.5 ml. Cellular immune response and safety were determined at various times during and after the therapy. In the course of treatment, virtually all the investigated immunoparameters were raised compared to the baseline values at the start of treatment. The statistically significant rises in the cell count of total lymphocytes, monocytes and natural killer (NK) cells was noteworthy. The differences in comparison with the baseline values at the various measuring times during treatment were up to 35%. In the first weeks of treatment at least, the raised cell count of NK cells correlated with the significantly increased cytotoxic activity versus tumor cells ex vivo. The NK factor (product of NK cells and ex vivo activity) was determined to assess the total NK activity more accurately, which rose up to 50% compared to the baseline value. Other lymphatic subpopulations, for instance CD3+, CD8+, CD3+CD4+ and CD3+CD8+ cells, also revealed distinct rises in cell count in the course of treatment. Within 6 weeks after completion of treatment, the overall values dropped again; but for a series of immunoparameters – in particular for the NK cells – they were still raised in comparison to the baseline values. The extensive laboratory diagnostics (haematology, clinical chemistry) showed that treatment with the standardized mistletoe extract PS76A2 was well tolerated by all patients. In single cases, local reactions at the injection sites were of a minor nature and reversible within two days. Summarizing, it can be stated that the standardized mistletoe extract PS76A2 significantly improved the immune status of tumor patients and was administered safely over a long period.

The Standardised Mistletoe Extract PS76A2 Improves QoL in Patients with Breast Cancer Receiving Adjuvant CMF Chemotherapy: A Randomised, Placebo-controlled, Double-blind, Multicentre Clinical Trial

V.F. SEMIGLASOV(1), V.V. STEPULA(2), A. DUDOV(3), W. LEHMACHER(4) and U. MENGS(5)
(1)Scientific Research Oncological Institute, St. Petersburg, Russia; (2)Regional Oncological Clinic, Odessa, Ukraine; (3)Sofia Cancer Centre, Sofia, Bulgaria; (4)University of Cologne, Cologne; (5)MADAUS AG, Cologne, Germany
Key Words: Standardised mistletoe extract, mistletoe lectin, breast cancer patients, chemotherapy, immunomodulation, quality of life.
Running Title: Mistletoe Extract Improves QoL in Cancer Patients
Correspondence to: Dr. Ulrich Mengs, MADAUS AG, D-51101 Cologne, Germany.
Tel: (+) 49-221-8998-251, Fax: (+) 49-221-8998-1251, e-mail: u.mengs@madaus.de
Abstract: Patients with breast cancer receiving adjuvant chemotherapy frequently suffer from a restricted quality of life (QoL) due to the side-effects of chemotherapy and consequences of coping with diagnosis. Therefore, the objective of this clinical study was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to the galactoside-specific mistletoe lectin, on QoL by performing a placebo-controlled trial. Overall, 272 patients with breast cancer receiving adjuvant CMF chemotherapy (cyclophosphamide-methotrexate-fluorouracil) were enrolled and randomised to groups receiving placebo or PS76A2 at concentrations of 10, 30 or 70 ng mistletoe lectin (ML) per ml. The patients received 0.5 ml study medication twice weekly subcutaneously for 15 consecutive weeks (4 CMF cycles). Primary variables were the self-assessment QoL scores GLQ-8 (Global Life Quality) and Spitzer’s uniscale. As a result, statistically significant effects on QoL were obtained with the medium dose (15 ng ML/0.5 ml). The treatment difference between the medium dose and placebo with regard to the GLQ-8 sum was 60.8 mm (95 % confidence interval: 19.3 to 102.0 mm). The treatment effect for Spitzer’s uniscale between the medium dose and placebo was 16.4 mm (95 % confidence interval: 6.3 to 26.6 mm). The results on QoL were supported by an increase of T helper lymphocytes (CD4+) and the CD4+/CD8+ ratio (p<0.05). Overall, PS76A2 was well tolerated. Local reactions at the injection sites occurred dose-dependently, but were of mild degree at the low and medium dose levels. In conclusion, the medium dose of PS76A2 (15 ng ML/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients.