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.
Ukrainian Research Institute of Oncology and Radiobiology
6th International Congress on Hormones and Cancer, September 5-9, 1999, Jerusalem, Israel
Russian version available here
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:
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:
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.