Relieving Mouth Sores from Cancer Treatment: The Discovery of Palifermin

Research and collaboration by NCI scientists resulted in the development of palifermin, a very successful treatment for preventing and treating mouth sores (known as oral mucositis). This drug vastly improves the quality of life for patients who are undergoing intensive cancer treatment.

Relief for Painful Mouth Sores Due to Cancer Treatment

Chemotherapy and radiation kill rapidly growing cells, including those in the mouth and hair. As a result, some cancer patients undergoing these treatments develop painful mouth sores and ulcers, called oral mucositis. This inflammation of the mucous membranes in the mouth and throat can cause considerable pain when eating, speaking, or drinking.

The sores also leave patients open to potentially life-threatening infections. Patients with severe mucositis may need intravenous nutrition, antibiotics to fight infections, pain medicines, and longer hospital stays. For years, doctors wondered what could be done to relieve oral mucositis in patients receiving cancer treatment.

A Chance Discovery Leads to a Possible Solution

In the late 1980’s, NCI scientists Jeffrey Rubin, M.D., Ph.D., Stuart Aaronson, M.D., and Paul Finch, Ph.D., were conducting research to identify proteins that play a role in cancer cell growth. They studied epithelial cells, which line the surfaces of the body’s organs, because many tumors are derived from these cells.

Instead of finding a culprit of uncontrolled cancer growth, the scientists identified and isolated another molecule, that they called keratinocyte growth factor (KGF), that turned out to be expressed in epithelial wounds.

Subsequent research showed that KGF aids the healing process by stimulating the growth of epithelial cells in tissues such as the skin and mouth. And additional research showed that treating cancer patients with KGF before cancer treatment had a strong protective effect, limiting the damage cancer treatments can inflict on the rapidly dividing cells of the mouth.

These studies suggested that KGF could potentially be used to treat or prevent oral mucositis.

NCI Collaboration Speeds Drug Development to Treat Mouth Sores

To speed the translation of this discovery from the laboratory to patients, NCI sought out a commercial partner to develop KGF into a drug treatment. In an example of a successful public-private partnership, NCI worked with Amgen, a biotechnology company, to develop the drug palifermin (Kepivance). Palifermin is a modified version of human KGF that is manufactured in a lab.

In a key clinical trial involving multiple NCI-designated cancer centers, over 200 cancer patients received either palifermin or a placebo with their cancer treatment. This study showed that, for patients with blood cancers who were receiving high-dose radiation and chemotherapy, those given palifermin had a much lower incidence of the most debilitating form of oral mucositis. Compared to patients who received placebo, patients who received palifermin also needed less pain medicine and intravenous nutrition.

Palifermin Improves Quality of Life for Cancer Patients

Based on these findings, in 2004, the Food and Drug Administration (FDA) approved palifermin for the treatment of oral mucositis in patients with blood cancers who are receiving intensive chemotherapy and radiotherapy followed by a stem cell (blood or bone marrow) transplant.

Currently, palifermin is only approved for use in patients with blood cancers. Additional studies have suggested that it is safe and effective in reducing severe oral mucositis in patients treated for other cancers, particularly head and neck cancers. NCI scientists are currently studying its use for other conditions, such as graft-versus-host disease (GVHD), a complication that occurs in bone marrow or stem cell transplant patients.

Because of NCI research, clinicians now have a remarkably successful treatment for preventing and treating oral mucositis, vastly improving the quality of life of patients who are undergoing intensive cancer treatment.