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Ketoprofen ‘a huge step forward’ for treatment of lymphedema symptoms

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The anti-inflammatory drug ketoprofen appeared to effectively treat lymphedema symptoms and ease the burden of care, according to study results.

“Ketoprofen restores the health and elasticity of the skin. … I believe it will reduce recurrent infection [and] can also reduce swelling,” Stanley G. Rockson, MD,professor of cardiovascular medicine at Stanford University School of Medicine, said in a press release. “This new treatment does not cure lymphedema, but our studies show it has the capacity to make the illness more livable and more workable.”

Lymphedema — a common condition that stems from a damaged lymphatic system — leads to swelling in one or more parts of the body. It typically affects the legs and arms.

Although lymphedema can be hereditary, it is common among patients with cancer who undergo lymph node-removing surgery.

Rockson and colleagues conducted two pilot trials to examine the safety and efficacy of ketoprofen among a small cohort of patients with lymphedema.

The first exploratory trial included 21 patients with primary or secondary lymphedema who received 75 mg ketoprofen three times daily. Researchers observed significant improvements in histopathology and skin thickness at 4 months compared with baseline.

Researchers then conducted a double-blind, placebo-controlled trial in which 34 patients with lymphedema received ketoprofen (n=16) or placebo (n=18). A change in skin thickness as measured by skin calipers served as the primary endpoint. Secondary endpoints included histopathology, limb volume, bioimpedance and systemic inflammatory mediators.

Results showed significant reductions in skin thickness with ketoprofen, as well as improvements in composite measures of histopathology, and decreases in plasma granulocyte-colony stimulating factor expression.

HemOnc Today spoke with Rockson about the trials, the clinical implications of the findings and next steps for research.

Question Can you explain the rationale for these trials?

Answer: I began this work in animal models more than 15 years ago. I wanted to understand what it is in the body that characterizes an abnormal response and leads to the development of lymphedema. This is where the animal model came into play. This led us to identify conclusively for the first time that tissue in lymphedema is expressing a profound inflammatory reaction, and the molecular signature of this appeared to be quite specific. We identified a specific pathway that we thought may be uniquely involved in allowing the lymphedema to express itself. Subsequent work allowed us to substantiate this initial impression. We learned that the byproduct of this inflammatory response was to block the lymphatics’ ability to repair themselves, and this probably represented the difference between those who develop lymphedema and those who do not. It also allowed us to identify specific drugs that may block this pathway from being activated in a targeted way.

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