Efficacy and tolerability
of proteolytic enzymes as an anti-inflammatory agent in lymphoedema
after axillary dissection due to mammary cancer
Kasseroller R., Wenning H.G. Efficacy
and tolerability of proteolytic enzymes as an anti-inflammatory
agent in lymphoedema after axillary dissection due to mammary
cancer. Czech abstract. The European Journal of Lymphology,
2002-2003, Vol. 10, No. 37-38, pp. 18-26,
Lymphoedema is a chronic disease caused by the damage of lymphatic
vessels due to surgical treatment and/or radiotherapy (secondary).
Another cause is the malformation or lack of lymphatic vesels
(primary).
The aim of the study was to demonstrate the efficacy and
tolerability of the proteolytic enzyme combination preparation
Wobenzym in additional reduction of arm volume (primary criterion)
in patients with secondary lymphedema after dissection of axillary
nodes due to mammary cancer. Secondary criteria were improvement of
the skinfold thickness, CRP values, tension, and global judgement of
the efficacy by both investigator and patient.
The study population comprised of 88 female patients aged between 30
and 80 with one sided secondary arm lymphedema after dissection of
the axillary lymph nodes (level I or II according to the St. Gallen
consensus conference) due to mammary cancer, who have been treated
with combined decongestive therapy. All patients received the
standard treatment - a combined decongestive therapy, comprising the
manual lymphatic drainage on affected sites with consecutive
bandaging of the affected arm and specially designed exercises and
skin care from day 1 to day 20. The test group of patients received
additionally Wobenzym at a dose of 5 coated tablets three times
daily over 6.5 weeks.
Both treatment groups were well comparable. The median time between
the lymph node dissection and the baseline visit was 47.5 months in
the Wobenzym group and 48 months in the placebo group.
For measuring the indicator volume reduction in arm lymphedema, a
Volometer was used. For the indicator tension, a four point rating
scale was used. All the measurements were carried out on days 1, 9,
19, and 45 (final visit). CRP value was measured on days 1 and 19.
On the ill arm both groups showed a decrease of volume until visit 4
(day 45). Both groups showed an almost identical course of the
volumetric development between baseline visit and final end point
visit, although there was a slight superiority of Wobenzym for the
development between visit 3 and 4 with regard to the percent changes
of –5% and more without statistical significance.
Both groups showed the greatest decrease of skinfold thickness
between visits 2 and 3 with a very similar development between
baseline visit and final visit with regard to the results of the ill
arm. The results of the
percent changes from baseline with regard to visit 2, 3, and 4
showed a mean reduction by –29.84% for the verum group and –15.73%
for placebo group. The development between visit 3 and 4 showed only
slight superiority for the verum group.
Both groups showed an almost similar decrease of tension in
the ill arm until visit 4. A percent change of 100 % (total
improvement) was reached by 62.79 % patients in the Wobenzym group
and by 47.62 % patients in the placebo group. The percent changes
between visits 3 and 4 – time where no concomitant combined
decongestive therapy was applied – showed a clear superiority of the
Wobenzym treated patients.
CRP was measured at visit 1 (baseline) and 3 (day 19). Wobenzym
group showed better results than placebo group with regard to the
CRP development between baseline visit and visit 3: out of 15
patients with high baseline findings five patients normalized in the
Wobenzym group.
There was a clear superiority for the verum group with regard to the
CRP development between visit 1 and 3.
Overall, 15 adverse events were recorded, 7 for the verum group and
8 for the placebo group. The adverse events in the verum group were
all gastrointestinal complaints of moderate intensity and rated as
possibly (6 cases) or definitely (1 case) related to the study
medication. All the patients showing adverse events completely
recovered without sequelae.
All in all, the study failed to demonstrate efficacy in
edema-related criteria (most likely due to extensive concomitant
physical therapy in all patients) but demonstrated efficacy of
Wobenzym with regard to the inflammation-related criteria. The
inflammation-related criteria showed more than small superiority of
Wobenzym. Moreover, for the subgroup “no chemotherapy” the
inflammation-related criteria showed
more than medium-sized superiority of Wobenzym. Reduced inflammatory
tissue conditions are the basis for minimizing fibrosis thus
preventing further inflammation and infection.