Phase I Study Evaluating the Safety of Bevacizumab in Women With a History of Breast Cancer Suffering From Moderate to Severe Upper Extremity Lymphedema
Lymphedema occurs with varying frequency in patients with cancer but approximately 10-15% of
all breast cancer patients will develop lymphedema following breast cancer treatment.
Lymphedema in breast cancer patients following axillary lymph node dissection is caused by
the interruption of the axillary lymphatic system by surgery or radiation therapy, which
causes an accumulation of fluid in the subcutaneous tissue of the arm, with decreased
distensibility of tissue around the joints and increased weight of the extremity. The
primary current therapy employed involves complete decongestive therapy (CDT) which
encompasses the use of manual lymphatic drainage (MLD) and compression bandaging (CB) to the
The specific contribution of the vascular system to the development of lymphedema is
unclear. Vascular permeability is a complex process which is primarily controlled by the
interaction of the ligand vascular endothelial growth factor (VEGF). As a result of the
understanding of the biology of VEGF and the anecdotal appreciation of women with lymphedema
who have noted improvement in their lymphedema while on VEGF inhibitor therapy, it is
hypothesized that the reduction in vascular permeability resulting from the use of a VEGF
inhibitor either alone or in conjunction with standard decongestive lymphedema therapy may
significantly improve the outcome for patients with this post-operative complication.
Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF.
Bevacizumab blocks the development of new blood vessels in cancer and it is approved by the
FDA for the treatment of colon cancer in combination with chemotherapy. While bevacizumab
has been administered to thousands of patients with cancer, there is only limited
information about the use of bevacizumab in subjects without active cancer.
This study will evaluate the safety profile of escalating doses of bevacizumab administered
intravenously alone for 4 weeks followed by 4 weeks of therapy in combination with manual
lymph drainage (MLD) and compression bandaging (CB) to patients with moderate to severe
unilateral upper extremity lymphedema due to prior breast cancer therapy.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Michael S Gordon, MD
Premiere Oncology of Arizona
United States: Food and Drug Administration
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