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

Phase 2
18 Years
Not Enrolling
Lymphedema, Breast, Cancer

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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.

Inclusion Criteria

Inclusion criteria:

- Unilateral (ipsilateral to breast cancer resection side) lymphedema of the upper

- Extravascular water ration of > 1.07/1 between affected vs. normal arm using multiple
frequency bioelectric impedence

- Patient is > 2months from last surgical or radiation treatment to the affected axilla

- Renal and hepatic function:

Creatinine clearance > 50ml/min, total bili <2 mg/dl, transaminases <1.5 x ULN

- Patient not pregnant or breastfeeding. Use of barrier contraception if sexually

- ECOG performance of 0-2

- Patient not allergic to pycnogenol

Exclusion criteria:

- Patients treated with their first course of chemotherapy or radiation

- Chemotherapy or radiation to axillary lymph node will exclude patients for 8 weeks
following treatment

- Patients with more than one episode of arm cellulitis, venous clot, or woody fibrosis
of the affected arm. Antibiotics used to treat cellulitis must be completed at least
4 weeks prior to initial screening

- Patients with a defibrillator Midazolam study only: Patients requiring or benefiting
from supplemental oxygen, patients allergic to cherries

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Principal Investigator

James F. Cleary, M.B.B.S.

Investigator Role:

Study Chair

Investigator Affiliation:

University of Wisconsin, Madison


United States: Federal Government

Study ID:

R21 AT001724-01



Start Date:

August 2003

Completion Date:

August 2007

Related Keywords:

  • Lymphedema
  • Breast
  • Cancer
  • lymphedema
  • breast
  • cancer
  • plant preparation
  • herbal preparation
  • pine bark extract
  • Breast Neoplasms
  • Lymphedema



University of Wisconsin Comprehensive Cancer Center and School of Pharmacy Madison, Wisconsin  53706