Efficacy and tolerability of proteolytic enzymes as an anti-inflammatory agent in lymphoedema after axillary dissection due to mammary cancer
Source:
The European
Journal of Lymphology, 2002-2003, Vol. 10, No. 37-38, pp. 18-26, author:
579 KA (1-10-2)
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. Out of 13 patients with high baseline
findings in the placebo group, only one patient normalized. For patients with
high CRP-values at baseline there has been mean percent change from baseline of
–39.8%, while in the placebo group –17.4%. 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.