Badger C, Preston N, Seers K, Mortimer P, et al.
The Cochrane database of systematic reviews. Date of publication 2004 Jan 1;volume (2):CD003140.
1. Cochrane Database Syst Rev. 2004;(2):CD003140.
Benzo-pyrones for reducing and controlling lymphoedema of the limbs.
Badger C, Preston N, Seers K, Mortimer P.
BACKGROUND: Lymphoedema is the accumulation of excess fluid in the body caused by
obstruction of the lymphatic drainage mechanisms. It can be caused by a number of
factors, including congenital predisposition, parasitic infection or surgery.
Lymphoedema is chronic and progressive and affects a significant proportion of
the population. The standard treatment regimes include compression hosiery, skin
care and exercise. The use of drugs in treatment, particularly benzo-pyrones, has
gained favour over the last ten years. Benzo-pyrones, originally developed for
use in vascular medicine, are prescribed to reduce vascular permeability and thus
the amount of fluid forming in the subcutaneous tissues. Advocates for this
treatment method believe that, as a result of reducing filtration, the drugs have
some beneficial effect on pain and discomfort in the swollen areas. Proponents
also claim that these drugs increase macrophage activity, encouraging the lysis
of protein, which in turn reduces the formation of fibrotic tissue in the
lymphoedematous limb.
OBJECTIVES: To assess the effectiveness of benzo-pyrones compared to placebo or
to different benzo-pyrones in reducing limb volume, pain and discomfort in
lymphoedematous limbs. To assess the effect of benzo-pyrones on the quality of
affected tissues and on the patient's quality of life and, finally, to establish
the incidence of adverse effects
SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register (September
2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists
produced by The British Lymphology Society, the National Research Register (NRR)
and The International Society of Lymphology congress proceedings.
SELECTION CRITERIA: Types of studies considered for review were randomised
controlled trials testing Paroven, coumarin, Venastat, Cyclo 3 Fort or Daflon
versus placebo (with both groups having or not having standard physical treatment
DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two
blinded reviewers who screened the papers independently using a checklist of
criteria relating to the randomisation and blinding of the trial. Both reviewers
extracted data from the eligible studies using a data extraction form.
MAIN RESULTS: Overall, 15 trials were included that evaluated the role of
benzo-pyrones. Three trials of oxerutin were found. Each tested the drug over 6
months using the same dose of drug against placebo. Two were crossover trials and
one a parallel group trial with a total number of 127 participants and data
available for only 81 of them. There were insufficient data provided in any of
the trials to calculate the per cent reduction or increase in baseline excess
limb volume. Standard deviations or confidence intervals and the numbers in the
groups at the different stages of the trial were missing for all the data in two
of the reports and for much of the data in the third, making any attempt at
meta-analysis impossible. One trial testing Cyclo 3 Fort (approved name) over 3
months was found and involved 57 patients but provided insufficient data to allow
a proper analysis of its findings. A single trial of Daflon (approved name) was
found, lasting 6 months and involving 104 participants; once again there was
insufficient information provided in the report to reach a conclusion about the
effectiveness of the drug. Three trials of coumarin combined with troxerutin were
found and tested two different doses of the drug against each other with no
placebo, however, numbers of participants in the trial groups and baseline data
were not provided. Eight trials of coumarin were identified. Two of the reports
were confirmed as reporting the same trial and a further trial potentially also
referred to the same trial but this was unconfirmed. A further two papers
appeared to refer to the same trial but this was not confirmed. Three trials
involved the same researcher. Five studies were conducted in India or China and
they added anti-filarial dia or China and they added anti-filarial drugs to the
interventions tested. The numbers of participants withdrawn and the numbers
included in the analyses in all these trials were not extractable; the reporting
of outcome measures in most of the trials was not clear. Loprinzi's 1999 trial in
the USA reported the conduct of the trial and its findings with more detail,
however, its conclusions were very much at odds with the findings of the other
trials, finding that no difference was observed between those on the active
preparation (coumarin) and placebo in any of the outcomes under investigation.
This trial also reported a case of hepato-toxicity in a patient receiving the
active preparation.
REVIEWERS' CONCLUSIONS: Meta-analysis was not performed due to the poor quality
of the trials. It is not possible to draw conclusions about the effectiveness of
Benzopyrones in reducing limb volume, pain, or discomfort in lymphoedematous
limbs from these trials.
DOI: 10.1002/14651858.CD003140.pub2
PMID: 15106192 [Indexed for MEDLINE]
