Systemic enzyme therapy in the complex treatment of breast cancer.
Tarutinov
V.I., Nosa P.P., Ros N.V., Galakhin K.A., Shpilevaja S.I. Systemic
enzyme therapy in the complex treatment of breast cancer. Ukrainian
Research Institute of Oncology and Radiobiology. 6th International
Congress on Hormones and Cancer, September 5-9, 1999, Jerusalem,
Israel
Breast cancer occupies a first
place among oncopathology in Ukrainian women. In many cases (up to
60%), cancer is diagnosed in the late stages, requiring chemo- and
radiotherapy in the neoadjuvant regime. Unfortunately, tumor is
often not sensitive enough to the radio- and chemotherapy. More than
50% of viable tumor tissue still outlasts. Combination of
radiotherapy and polychemotherapy reduces viable tumor tissue to
40%. However, the efficacy of radiotherapy followed by
polychemotherapy decreases because of postirradiation reactions -
fibrous changes, edema, development of "protective" lymphocytary
fornix surrounding the tumor. Therefore, systemic enzyme therapy is
necessary to facilitate a contact between the tumor and
chemo-preparation. Over the recent years, systemic enzyme therapy
has become an essential part of treatment of both breast cancer and
dyshormonal hyperplasias. Very important is the capacity of enzymes
to act as "carrier" helping to transport chemo-preparations to the
target place.
Furthermore, enzymes are able to reduce number and severity of toxic
complications developing during chemo- and radiotherapy. A "fornix"
surrounding the tumor prevents from the effect of
chemo-preparations. Additionally, macromolecules and fat-soluble
compounds penetrate more easily to the tumor tissue in comparison to
the normal one. Therefore, enzymes can facilitate the effect on the
tumor. Additionally, macromolecules and fat-soluble compounds
penetrate more easily to the tumor tissue in comparison to the
normal one. Therefore, enzymes can facilitate the effect on the
tumor. Enzymes destroy the net which connects tumor cells with each
other and with endothelium, realize a proteolysis of tumor cell
membranes. Consequently, tumor size is reduced, tumor necrosis
occurs, and tumor is more easily attainable for chemo- and
hormone-preparations. Results of experimental and clinical studies
(Zeneca and Pur, 1964) have shown that proteinases increase tissue
permeability. Moreover, enzymes slow down formation of immune
complexes and show an indirect immunoregulatory effect (Kunze, 1993,
1995). Currently, attention has been focused on dynamics of TGF-?
alterations under the effect of enzymes.
Overproduction of TGF-? leads to the undesirable postirradiation
changes and enhances development of fibrous tissue. Administration
of proteinases (Phlogenzym) decreases TGF-? level and reduces
fibrous changes (Heidland, 1997). Thus, systemic enzyme therapy
appears to be suitable for the treatment of fibrous forms of
hyperplasias.
We observed 55 patients with breast cancer, II-IV clinical stage (T
2-4 N 1-3 M 0), aged 35-64 years. All patients were subject to the
complex treatment, including enzyme preparations Wobe-Mugos and
Wobenzym (Mucos Pharma, Germany). Patients received in the
preoperative period neoadjuvant course of polychemotherapy with
respect to the tumor sensitivity towards chemo-preparations (method
according to Kulik). In most of the cases, the treatment schemes
were CMF (cyclophosphamide, methotrexate, 5-fluorouracil) or CAF (cyclophosphamide,
Adriablastin-doxorubicin, 5-fluorouracil). At the same time patients
received Wobe-Mugos, 3-5 tablets 3 times a day, 1 hour before meals.
After neoadjuvant polychemotherapy (1-3 days), a radical surgery was
performed (depending on the volume from quandrantectomy to
mastectomy, according to Halstedt). The effect of neoadjuvant
polychemotherapy was evaluated by morphometry: comparison was done
with tumors of analogous patients which received neoadjuvant
polychemotherapy without systemic enzyme therapy and which also
received radiotherapy. Volume of viable tumor tissue remained in the
control group 50%, in the group with neoadjuvant polychemotherapy
without enzymes 40%, and in the group with enzyme therapy up to 34%.
In the postoperative period, development of postirradiation
dermatitis, lymphostasis and lymphorhea, as well as healing of
surgical wounds, volume of viable tumor tissue were observed and
evaluated in comparison to the control. It was found that complex
treatment of breast cancer, including neoadjuvant chemo- and
hormone-therapy and systemic enzyme therapy showed less
complications and also smaller volume of viable tumor tissue (by
15-16%), as compared to the control group. This corresponds to the
decrease of TGF-? during administration of enzyme therapy.
Therefore, preparations of systemic enzyme therapy were successfully
used as "supportive" ones during chemotherapy. The main chemotherapy
side-effects are:
immunodepressive effect, impaired function of liver, kidneys,
neurological damage, hemopoiesis suppression, dyspeptic complaints.
The effects of enzymes include:
Immunomodulatory effect;
Decrease of hepatotoxicity and pneumotoxicity;
Improvement of rheological properties of blood and microcirculation;
Normalization of cytokine concentration which enables an increased
efficacy of chemotherapy.
Our results showed a decrease of postirradiation reactions in 20 out
of 31 patients.
Lymphedema is caused by the lymph stagnation which is developed as a
result of obliteration of deep lymphatic vessels and local
compensatory mechanism disorders. Plasma, rich on proteins,
penetrates to the surrounding tissues, causing a development of
fibrous and sclerotic changes. Wobenzym positively influences this
complication thanks to the following mechanisms:
Antiinflammatory and antiedematous effect of proteinases
Degradation of inflammatory products
Normalization of equilibrium between fibrin formation and cleavage
on the vessel
walls.
Hydrolases, causing breakdown of proteins and detritus, decrease the
exsudate viscosity and, therefore, improve its liquid properties.
Rutin shows antihemorrhagic effect, decreases capillary
permeability, and by strengthening of vessel walls prevents
development of edemas, rich on proteins.
Lysis of complex macromolecules reduces oncotic pressure, small
residues are removed through lymphatic system.
Wobenzym causes edema reduction and its resorption. Thus, pain
syndrome caused by a tension also decreases.
Recommended dosage (lymphedema prophylaxis): preoperatively
Wobe-Mugos, 3 tablets 3 times a day for 2 weeks, postoperatively
Wobenzym 5 dragees 3 times a day.