Trial Information

Pycnogenol for the Treatment of Lymphedema of the Arm in Breast Cancer Survivors

Lymphedema of the arm affects the function and self-image of approximately 600,000 of the 2
million breast cancer survivors in the United States. Chronic lymphedema can lead to
recurrent infections and permanent swelling, in some cases impairing function. Although
various methods of massage and the use of non-elastic compression "sleeves" have been shown
to decrease the severity of lymphedema, these methods of physical therapy are limited in
terms of patient acceptance, compliance, and by the availability of trained therapists.
There is presently no pharmacologic treatment that has proven effective in treating or
preventing the development of lymphedema in women treated for breast cancer. This is a
double-blind, placebo-controlled trial of an extract of the bark of the French maritime pine
tree (Pycnogenol(r)) as a treatment for arm lymphedema in breast cancer survivors.
Pycnogenol(r) is widely used in Europe for lymphedema of the leg and varicose veins, and is
thought to act by several mechanisms including vascular permeability and vascular
constriction. The development of such a therapeutic approach would therefore constitute a
major breakthrough in the treatment of this common symptom of breast cancer lymphedema.
Bioelectric impedance is a painless, quick, and easily-performed method of estimating the
extracellular and total water volume of the body or segment, such as the arm. We will
compare the correlation of both a single- and a multiple-frequency bioelectric impedance
instrument in measuring change in arm volume to a standard assessment using water
displacement. We expect that bioelectric impedance will prove faster and more sensitive to
changes in extracellular water (lymphedema) than the water displacement method. We also
propose to use a small oral dose of midazolam and single blood sampling to screen for
effects of Pycnogenol(r) on the activity of the common drug metabolizing enzyme CYP3A4. For
those subjects who are already receiving digoxin, we will use digoxin urine excretion to
screen for effects of the botanical upon the activity of P-glycoprotein. Finally, we will
continue the evaluation of a new questionnaire of lymphedema symptoms presently being tested
as a tool for assessing the severity and improvement of symptoms with treatment. In summary,
the successful completion of this research can be expected to provide an alternative therapy
and new instruments for treating and measuring lymphedema.