Systemic Enzyme Therapy in Oncology
Effect and Mode of Action

Leipner J., Saller R.

Department of Natural Medicine, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland

Drugs 2000 Apr, Vol.59, No. 4, pp. 769-780 - ISSN 0012-6667

SO 128 (2-03-2)

Abstract

Plant extracts with a high content of proteolytic enzymes have been used for a long time in traditional medicine. Besides proteolytic enzymes from plants, 'modern' enzyme therapy additionally includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is partly based on scientific studies and is partly empirical. The aim of the current review is to provide an overview of clinical trials of systemic enzyme therapy in oncology, and to discuss the evidence for their possible mechanisms of action.
Clinical studies of the use of proteolytic enzymes in oncology have mostly been carried out on an enzyme preparation consisting of a combination of papain, trypsin and chymotrypsin. This review of these studies showed that enzyme therapy can reduce the adverse effects caused by radiotherapy and chemotherapy. There is also evidence that, in some types of tumours, survival may be prolonged.
The beneficial effect of systemic enzyme therapy seems to be based on its anti-inflammatory potential. However, the precise mechanism of action of systemic enzyme therapy remains unsolved. The ratio of proteinases to antiproteinases, which is increasingly being used as a prognostic marker in oncology, appears to be influenced by the oral administration of proteolytic enzymes, probably via an induction of the synthesis of antiproteinases. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes, which might be an indication of the efficacy of enzyme therapy. Effects on adhesion molecules and on antioxidative metabolism are also reviewed.
Plant extracts with a high content of proteolytic enzymes have been used for a long time in the traditional medicine of Central and South America.^[1,2] Systemic enzyme therapy is currently being studied for a variety of indications. Its therapeutic use is based partly on scientific studies and is partly empirical. The fact that systemic enzyme therapy has found a special place in oncology is, in part, explained by historical factors. The foundations of 'modern' enzyme therapy can he found in a book by the English physician John Bard, published in 1907 under the title of 'The Enzyme Treatment of Cancer and its Scientific Basis'. After Adolf Gaschler had developed the anticancer agent Cardozelan, based on chymotrypsin, Max Wolf and Helene Benitez carried out systematic research in the mid-1950s leading to the development of an 'optimised combination' of plant and animal proteinases, which in their view possessed an optimal anti-cancer effect. The principle of enzyme combinations, developed by Wolf and Benitez, continues to find application today, admittedly sometimes in the form of preparations that differ from the original enzyme combination preparation (WoBe). In adjuvant or palliative cancer therapy, oral enzyme therapy has generally been found to be a well tolerated form of treatment for the relief of adverse effects caused by other tumour therapies and for improving quality of life.
The aim of the current paper is to provide an overview of clinical trials of systemic enzyme therapy in oncology, and to discuss the evidence for possible mechanisms of action of this form of therapy from these clinical studies and experimental studies. The literature search was based on the Medline (l966-1999), EMBASE (1980-1999) and AMED (Allied and Alternative Medicine, 1985-1999) databases. In addition, the firm MUCOS (Geretsried, Germany) allowed us to examine data from unpublished studies.