Effect of a perioperative infusion of mistletoe extract on surgery-induced immunosuppression in colorectal cancer patients

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Phytomedicine 14 (2007) VII 40 www.elsevier.de/phymed

35. Effect of a perioperative infusion of mistletoe extract on surgery-induced immunosuppression in colorectal cancer patients M. Schinka,, W. Tro¨gerb, A. Dabidiand, A. Goyertc, H. Scheuereckerd, J. Meyere, I.U. Fischerf, F. Glaserd a

Research Department, Verein Filderklinik e.V., Im Haberschlai 7, D-70794 Filderstadt, Germany Klinische Forschung Dr. Tro¨ger, Bo¨cklerstr. 5, 79110 Freiburg i. Br., Germany c Department of Internal Medicine, Filderklinik, Im Haberschlai 7, D-70794 Filderstadt, Germany d Department of Surgery, Filderklinik, Im Haberschlai 7, D-70794 Filderstadt, Germany e Department of Anaesthesiology and Intensive Medicine, Filderklinik, Im Haberschlai 7, D-70794 Filderstadt, Germany f Bu¨ro fu¨r Biostatistik, Burgunderweg 36, D-72070 Tu¨bingen, Germany b

Major cancer surgery suppresses immune defence mechanisms, which is potentially harmful by promoting haematogenic tumour cell dissemination. Mistletoe extracts, on the other hand, are known to stimulate various parts of the immune system including natural killer (NK) cell cytotoxic activity. Therefore, the effect of a perioperative infusion of a standardized mistletoe preparation (Iscadors) on immune functions was tested in a prospective, sequential, randomized, open-label clinical trial. Patients with colorectal carcinoma undergoing open tumour resection were randomly assigned to either mistletoe infusion or no additional therapy. Our hypotheses were that after a mistletoe infusion, NK cell activity and expression of MHC class II antigen HLA-DR on monocytes would be less suppressed 24 h and 7 days after surgery, respectively. For statistical analysis a sequential study design was used. For the two triangular tests decision boundaries were calculated under the following assumptions: a relative difference between the two groups of 10% in NK cell activity and in HLA-DR-expression, respectively, and significance levels of a ¼ 0.025, which resulted in a sample size of 62 patients. Patient enrolment had to be stopped prematurely because both parameters exceeded the decision boundaries in the triangular test before the whole planned number of patients was recruited. Control patients showed a significant perioperative decrease of NK cell activity (44.4% 24 h after surgery) whereas mistletoe patients were not suppressed (NK cell activity: 7.9% 24 h after surgery). The group difference of 36.5% is significant (p ¼ 0.027). No group differences could be found for the HLA-DR-expression on monocytes: in both groups a significant perioperative decrease was detected. This study shows that a perioperative infusion of mistletoe extracts can prevent surgery-induced suppression of NK cell activity in colorectal cancer patients. The impact on relapse and survival should now be tested in further studies. Keywords: Randomized controlled trial; Colorectal cancer; Mistletoe; NK cell activity; HLA-DR; Monocytes

Corresponding author. Tel.: +49 711 7703 3601; fax: +49 711 7703 3630.

E-mail address: m.schink@filderklinik.de (M. Schink). 0944-7113/$ - see front matter doi:10.1016/j.phymed.2007.07.039