Relieving Oral Mucositis, a Serious Side Effect of Cancer Treatment: The Discovery of Palifermin

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Key Points

  • Oral mucositis, an inflammation of the mucous membranes in the mouth and throat, is a potentially serious side effect of chemotherapy and radiotherapy.
  • Palifermin, a drug initially developed by National Cancer Institute (NCI) scientists, has been shown to prevent and treat this condition, which increases the quality of life for cancer patients undergoing intensive treatment.
  • Multiple NCI-designated cancer centers participated in the clinical trial that led to FDA approval of palifermin. Palifermin is currently approved for use in patients with blood-system cancers, but other studies have suggested that it may be safe and effective in cancer patients treated for solid tumors.
  • NCI is planning to conduct a clinical trial to test whether palifermin can decrease graft-versus-host disease (GVHD), a complication that can occur after a stem cell or bone marrow transplant.
  • Continued support of a wide range of research activities, including a focus on preventing and treating oral mucositis, is needed to advance the science behind cancer prevention and care.

Pathway to Discovery

Patients with some types of cancer undergoing intensive treatment may develop oral mucositis, an inflammation of the mucous membranes in the mouth and throat. This can cause painful sores and ulcers, preventing a patient from eating, speaking, or drinking without considerable pain. The sores also leave patients open to systemic, potentially life-threatening infections. In cases of severe mucositis, patients may require intravenous nutrition, antibiotic therapy to combat infection, pain management, and prolonged hospitalization.

Photo of Jeffrey S. Rubin, M.D., Ph.D.
Jeffrey S. Rubin, M.D., Ph.D., of NCI’s Center for Cancer Research, with equipment that was used to purify keratinocyte growth factor (KGF), the native form of palifermin.

In the late 1980s, three NCI scientists, Jeffrey Rubin, M.D., Ph.D., Sturat Aaronson, M.D., and Paul Finch, Ph.D., were looking to identify growth-stimulating proteins specific to tumor cells. Because many tumors are derived from epithelial cells, researchers suggested that if they could isolate a protein that stimulates cancer growth, they might be able to control or reverse its effects.

Rather than finding the culprit behind uncontrolled cancer cell growth, they found increased levels of KGF messenger RNA, an RNA molecule that creates a chemical "blueprint" for protein production, in epithelial wounds, suggesting that KGF plays a role in wound repair. Subsequent research demonstrated that KGF not only helped the healing process, but pretreatment with KGF had a remarkable protective effect, limiting the cellular damage that normally results from exposure to a variety of toxic agents.

To allow the discovery to leapfrog from the laboratory to the patient, NCI sought out a commercial partner to further develop KGF. In an example of a successful public-private partnership, NCI worked with Amgen, a biotechnology company, to develop the drug in its current form, palifermin (Kepivance), a recombinant version of the naturally occurring KGF.  

Enhancing Cancer Care

Three intravenous lines and bags of a commonly used form of liquid nutrition.
Patients suffering from severe oral mucositis may need intravenous nutrition (depicted here), an intervention that palifermin helps patients avoid.

In a pivotal clinical trial, 212 cancer patients received either palifermin or a placebo with their treatments. The results of the palifermin-treated group were revolutionary in terms of quality of life, as the drug markedly reduced the incidence of the most debilitating form of oral mucositis, in which receiving nourishment orally is impossible. Also, the amount of pain medication required was significantly less in the palifermin group than in the placebo group, as was the need for intravenous supplemental nutrition.

Based on these findings, in 2004, the FDA approved palifermin for the treatment of oral mucositis in patients with leukemia, lymphoma, or multiple myeloma receiving intensive chemoradiotherapy followed by a stem cell (blood or bone marrow) transplant.

Turning Discovery into Health

Palifermin is currently only approved for use in patients with blood-system cancers. Additional studies have suggested that it is safe and effective in reducing severe oral mucositis in cancer patients treated for solid tumors, such as head and neck cancers, as well as sarcomas. Further study may lead to regulatory approval for its use in these cases.

Palifermin's clinical application may not be limited to oral mucositis. Researchers have been exploring its ability to prevent xerostomia (dry mouth), a significant chronic side effect of intensive cancer therapy that interferes with eating and makes patients susceptible to infection. Clinical trials also have been launched to test the safety and efficacy of palifermin in the management of acute lung injury.

Other clinical trials are exploring the use of palifermin to expedite the recovery of immune function or to reduce the severity of graft-versus-host disease (GVHD)—a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the transplant recipient’s body—which is potentially fatal. Researchers are hopeful that with further study palifermin can be used as an adjunct therapy in multiple clinical settings.

Research to Practice: NCI's Role

NCI scientists first discovered and isolated KGF and were also first to produce a biologically active recombinant KGF, palifermin. In addition, multiple NCI-designated cancer centers participated in the phase III clinical trial that led to FDA approval of palifermin. As of 2014, Ronald Gress, M.D., an NCI scientist, is planning to conduct a clinical trial to test whether palifermin can decrease GVHD risk in patients receiving blood stem cell transplants.

Key Takeaway

Clinicians now have a remarkably successful treatment for preventing and treating oral mucositis, vastly improving patients' quality of life who are undergoing intensive cancer treatment.

Selected Resources

Finch PW, Rubin JS. Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair. Adv Cancer Res. 2004;91:69-136.[PUBMED Abstract]

Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science. 198918;245(4919):752-755. [PUBMED Abstract]

Kapoor S. Emerging new clinical applications for palifermin: beyond its use in oral mucositis and graft versus host disease. Biologics. 2012;6:135-136. [PUBMED Central]

National Cancer Institute. Cancer Drug Information: FDA Approval for Palifermin. http://www.cancer.gov/about-cancer/treatment/drugs/fda-palifermin

Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA. Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA. 1989;86(3):802-806. [PUBMED Central]

Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004;351:2590-2598. [PUBMED Abstract]

Vadhan-Raj S, Goldberg JD, Perales M-A, Berger DP, van den Brink MRM. Clinical applications of palifermin: amelioration of oral mucositis and other potential indications.J Cell Mol Med. 2013;17(11):1371-1384. [PUBMED Abstract]

  • Posted: March 7, 2014